We claim:
1. A method for preparing a compound of formula (I):
(I)
wherein the method comprising reacting a compound of formula (I’’’):
with a compound of formula (KRM-C1)
, wherein X is Br, Cl or I; Y is -B(OH)2 or
optionally substituted with 1, 2, 3 or 4 independently selected C1-4 alkyl substituents,
wherein the subscript n is 1 or 2.
2. The method of claim 1, wherein the compound of formula (I’’’) is prepared by reacting a
compound of formula (KRM-A1): with a compound of formula (KRMB): wherein X is Br, Cl or I.
3. The method of claim 2, wherein the compound of formula (KRM-A1) is prepared by a
method comprising:
Ref: 27207-IN
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a) reacting a compound of formula (KRM-A2): with (1R,2R)-
cyclohexane-1,2-diamine to form a salt of formula: ;
b) recrystallizing the salt (5) to obtain salt (6) of formula: ;
and
c) treating the salt of formula (6) with an acid to obtain the compound of formula (KRMA1).
4. A method for preparing a compound of formula (I):
(I)
wherein the method comprising:
i. reacting a compound of formula (1) with a compound of formula
(2) to afford a salt of a formula (3) ;
Ref: 27207-IN
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ii. recrystallizing the salt of formula (3) in a solvent (B) to obtain a salt of a formula
(4) ;
iii. treating a mixture comprising the salt of formula (4) and a solvent (C) with an acid
to generate compound of formula (KRM-A) ;
iv. reacting the compound of formula (KRM-A) with a compound of formula (KRMB) to afford a compound of formula (I’): ;
and
v. reacting the compound of formula (I’) with a compound of formula (KRM-C)
to obtain the compound of formula (I).
5. The method of claim 4, wherein the step i) is carried out in the presence of the solvent (A)
selected from acetone, dichloromethane, n-propyl acetate, acetonitrile, methanol, isopropyl
alcohol, isopropyl acetate, isobutanol, 2-butanol, 1-butanol, n-butyl acetate, 1-pentanol, 1-
propanol, chloroform, methyl acetate, isobutyl acetate, isobutanol, ethanol, water, or
mixtures thereof.
6. The method of claim 4, wherein the solvent (B) is acetone, acetonitrile, methanol,
isopropyl alcohol, isopropyl acetate, isobutanol, 1-pentanol, 1-propanol, ethanol, water,
or mixtures thereof.
7. The method of any one of claim4, wherein the solvent (C) is acetone, dichloromethane,
n-propyl acetate, acetonitrile, methanol, isopropyl acetate, isobutanol, 2-butanol, 1-
butanol, n-butyl acetate, 1-pentanol, 1-propanol, chloroform, methyl acetate, isobutyl
acetate, isobutanol or ethanol.
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8. The method of claim 4, wherein the compound of formula (I’) is prepared by reacting a
compound of formula (II’): with a deprotecting agent.
9. The method of claim 8, wherein the compound of formula (II’) is prepared by i) reacting
the compound of formula (KRM-A) with oxalyl chloride to generate a compound of
formula (KRM-D); and ii) reacting the compound of formula
(KRM-D) in situ with the compound of formula (KRM-B).
10. A compound of formula (III)
(III); wherein
R
2
is halo, methylsulfonyloxy, p-tolylsulfonyloxy, phenylsulfonyloxy or
trifluoromethylsulfonyloxy.
11. The compound of any one of claims 10, having the structure:
(KRM-A).
12. A compound of formula (IV):
(IV), wherein:
R
1
is C1-6 alkyl; and R2
is halo, methylsulfonyloxy, p-tolylsulfonyloxy,
phenylsulfonyloxy or trifluoromethylsulfonyloxy.
13. The compound of any one of claims 12, having the structure: