(R)-2-(3-(1-bromo-8-methylimidazo[1,5-a]pyrazin-3-yl)pyrrolidin-1-yl)-N,N-dimethylacetamide → (R)-N-(4-(3-(1-(2-(dimethylamino)-2-oxoethyl)pyrrolidin-3-yl)-8-methylimidazo[1,5-a]pyrazin-1-yl)-2-methoxyphenyl)-4-methoxy-1-methyl-1H-indole-2-carboxamide

HRID 245725Notes

Reaction equation

HRID 245725 reaction equation
Br[C:2]1[N:3]=[C:4]([C@@H:12]2[CH2:16][CH2:15][N:14]([CH2:17][C:18]([N:20]([CH3:22])[CH3:21])=[O:19])[CH2:13]2)[N:5]2[CH:10]=[CH:9][N:8]=[C:7]([CH3:11])[C:6]=12.[CH3:23][O:24][C:25]1[CH:33]=[CH:32][CH:31]=[C:30]2[C:26]=1[CH:27]=[C:28]([C:35]([NH:37][C:38]1[CH:43]=[CH:42][C:41](B3OC(C)(C)C(C)(C)O3)=[CH:40][C:39]=1[O:53][CH3:54])=[O:36])[N:29]2[CH3:34]>>[CH3:21][N:20]([CH3:22])[C:18](=[O:19])[CH2:17][N:14]1[CH2:15][CH2:16][C@@H:12]([C:4]2[N:5]3[CH:10]=[CH:9][N:8]=[C:7]([CH3:11])[C:6]3=[C:2]([C:41]3[CH:42]=[CH:43][C:38]([NH:37][C:35]([C:28]4[N:29]([CH3:34])[C:30]5[C:26]([CH:27]=4)=[C:25]([O:24][CH3:23])[CH:33]=[CH:32][CH:31]=5)=[O:36])=[C:39]([O:53][CH3:54])[CH:40]=3)[N:3]=2)[CH2:13]1

Participants

3

Reactant 2

HCID 67364023(R)-2-(3-(1-bromo-8-methylimidazo[1,5-a]pyrazin-3-yl)pyrrolidin-1-yl)-N,N-dimethylacetamideHCID 673656514-methoxy-N-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-methyl-1H-indole-2-carboxamide

Product 1

HCID 53344863(R)-N-(4-(3-(1-(2-(dimethylamino)-2-oxoethyl)pyrrolidin-3-yl)-8-methylimidazo[1,5-a]pyrazin-1-yl)-2-methoxyphenyl)-4-methoxy-1-methyl-1H-indole-2-carboxamideYield 91.1%

Procedure

Reaction of (R)-2-(3-(1-bromo-8-methylimidazo[1,5-a]pyrazin-3-yl)pyrrolidin-1-yl)-N,N-dimethylacetamide (22 mg) and 4-methoxy-N-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-methyl-1H-indole-2-carboxamide (23 mg) according to the procedure described in example 4 step 4c and purification using prep-HPLC (column Luna C18(2); gradient acetonitrile/water with constant 0.003M trifluoroacetic acid) gave (R)—N-(4-(3-(1-(2-(dimethylamino)-2-oxoethyl)pyrrolidin-3-yl)-8-methylimidazo[1,5-a]pyrazin-1-yl)-2-methoxyphenyl)-4-methoxy-1-methyl-1H-indole-2-carboxamide (28.6 mg).

Workup

  1. customdescribed in example 4 step 4c and purification

Sources & evidence

ORD record
ord-0882485778f040ea85c74760fa8263d6
Source dataset
uspto-grants-2014_02
Patent number
US08658794B2

Reaction notes

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