Ethyl Bromide → Cis pyrazolo[1,5-a]pyrimidine-3-carboxylic acid {3-(5-chloro-2-difluoromethoxyphenyl)-1-[2-(5 ethyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-2-oxoethyl]-1H-pyrazol-4-yl}amide hydrochloride

HRID 529757ノート

反応式

HRID 529757 の反応式
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:36][CH:37]([F:39])[F:38])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])=[CH:11][N:10]([CH2:25][C:26]([N:28]3[CH2:35][C@@H:34]4[C@@H:30]([CH2:31][NH:32][CH2:33]4)[CH2:29]3)=[O:27])[N:9]=2)[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:47][CH3:48]>C(#N)C>[ClH:1].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:36][CH:37]([F:39])[F:38])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])=[CH:11][N:10]([CH2:25][C:26]([N:28]3[CH2:29][C@@H:30]4[C@@H:34]([CH2:33][N:32]([CH2:47][CH3:48])[CH2:31]4)[CH2:35]3)=[O:27])[N:9]=2)[CH:7]=1

参加物

5

反応物 3

HCID 6332Ethyl BromideHCID 11430Potassium CarbonateHCID 118522653Cis-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid {3-(5-chloro-2-difluoromethoxyphenyl)-1-[2-(hexahydropyrrolo[3,4-c]pyrrol-2-yl)-2-oxoethyl]-1H-pyrazol-4-yl}amide

生成物 1

HCID 131735621Cis pyrazolo[1,5-a]pyrimidine-3-carboxylic acid {3-(5-chloro-2-difluoromethoxyphenyl)-1-[2-(5 ethyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-2-oxoethyl]-1H-pyrazol-4-yl}amide hydrochloride

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
50 °C

実験手順

To a solution of cis-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid {3-(5-chloro-2-difluoromethoxyphenyl)-1-[2-(hexahydropyrrolo[3,4-c]pyrrol-2-yl)-2-oxoethyl]-1H-pyrazol-4-yl}amide (100 mg, 0.18 mmol) in acetonitrile (4 mL) was added potassium carbonate (37 mg, 0.27 mmol) and bromoethane (20 μL, 0.27 mmol). The reaction was heated at 50° C. for 2 hours and then allowed to cool to room temperature. The mixture was applied directly to an SCX-2 cartridge. Elution with 2M ammonia in MeOH gave the desired product. The product was purified by HPLC (Method 1) and the pure fractions were combined as passed through an SCX-2 cartridge. Elution with 2M ammonia in MeOH gave the free base on evaporation of the solvent. The solid was dissolved in 1.25M methanolic HCl and then the volatiles were evaporated. The HCl salt was crystallised from MeOH/Et2O and obtained as a white solid (32 mg, 40%). LCMS (Method 5) [M+H]+=585.0, RT=2.88 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 10.44 (d, 1H, J=35.0 Hz), 9.79-9.74 (m, 1H), 9.35 (dd, 1H, J=1.3, 7.0 Hz), 8.69 (dd, 1H, J=1.5, 4.2 Hz), 8.67 (s, 1H), 8.31 (d, 1H, J=3.8 Hz), 7.64 (dd, 1H, J=2.5, 8.8 Hz), 7.57 (d, 1H, J=2.6 Hz), 7.47 (d, 1H, J=8.9 Hz), 7.30 (dd, 1H, J=4.3, 7.0 Hz), 7.27 (t, 1H, J=73.6 Hz), 5.22-5.10 (m, 2H), 3.43 (s, 12H), 3.84-2.77 (m, 12H), 1.29-1.19 (m, 3H).

後処理

  1. temperatureto cool to room temperature
  2. washElution with 2M ammonia in MeOH

出典と根拠

ORDレコード
ord-2767ec13e77046aca5f4326836e9a4c7
出典データセット
uspto-grants-2016_05
特許番号
US09346815B2

反応ノート

読み込み中…