Diisopropylethylamine → 2-(3-chloro-6-fluoro-imidazo[1,5-a]pyridin-1-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide

HRID 245867ノート

反応式

HRID 245867 の反応式
[Cl:1][C:2]1[N:6]2[CH:7]=[C:8]([F:11])[CH:9]=[CH:10][C:5]2=[C:4]([C:12]2[N:13]=[C:14]3[C:20]([C:21]([OH:23])=O)=[CH:19][N:18]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:15]3=[N:16][CH:17]=2)[N:3]=1.Cl.[CH3:33][O:34][CH2:35][C@@H:36]([NH2:38])[CH3:37].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>O.CN(C=O)C>[CH3:33][O:34][CH2:35][C@@H:36]([NH:38][C:21]([C:20]1[C:14]2[C:15](=[N:16][CH:17]=[C:12]([C:4]3[N:3]=[C:2]([Cl:1])[N:6]4[CH:7]=[C:8]([F:11])[CH:9]=[CH:10][C:5]=34)[N:13]=2)[N:18]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:29])([CH3:30])[CH3:31])[CH:19]=1)=[O:23])[CH3:37]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 54596079(S)-1-methoxypropan-2-amine hydrochlorideHCID 712803452-(3-chloro-6-fluoro-imidazo[1,5-a]pyridin-1-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

生成物 1

HCID 712881612-(3-chloro-6-fluoro-imidazo[1,5-a]pyridin-1-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide収率 44%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

A round-bottomed flask was charged with 2-(3-chloro-6-fluoro-imidazo[1,5-a]pyridin-1-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (90 mg, 0.16 mmol) and (S)-1-methoxypropan-2-amine hydrochloride (40 mg, 0.32 mmol). DMF (1 ml) was added followed by N,N-diisopropylethylamine (0.1 ml, 0.57 mmol) and HATU (71 mg, 0.19 mmol). The reaction mixture was stirred at room temperature overnight then water was added. The resulting suspension was filtered, washing with water and petroleum ether. The brown powder was chromatographed over silica gel with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-2% MeOH) to afford 37 mg (44%) of 2-(3-chloro-6-fluoro-imidazo[1,5-a]pyridin-1-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide as a yellow solid.

後処理

  1. filtrationThe resulting suspension was filtered
  2. washwashing with water and petroleum ether
  3. customThe brown powder was chromatographed over silica gel with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-2% MeOH)

出典と根拠

ORDレコード
ord-e386c90466514b459b763b40def97a9b
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

読み込み中…