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Potassium Carbonate → [3-(4-{3-(5-Chloro-2-difluoromethoxyphenyl)-4-[(pyrazolo[1,5-a]pyrimidine-3-carbonyl)amino]pyrazol-1-yl}piperidin-1-yl)propyl]carbamic acid tert-butyl ester

HRID 529766
ノート
印刷プレビュー

反応式

HRID 529766 の反応式
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:31][CH:32]([F:34])[F:33])=[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]([CH:25]3[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)[N:9]=2)[CH:7]=1.[C:35]([O:39][C:40](=[O:46])[NH:41][CH2:42][CH2:43][CH2:44]Br)([CH3:38])([CH3:37])[CH3:36].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[C:35]([O:39][C:40](=[O:46])[NH:41][CH2:42][CH2:43][CH2:44][N:28]1[CH2:27][CH2:26][CH:25]([N:10]2[CH:11]=[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])[C:8]([C:6]3[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=3[O:31][CH:32]([F:33])[F:34])=[N:9]2)[CH2:30][CH2:29]1)([CH3:38])([CH3:37])[CH3:36]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 4460490tert-butyl N-(3-bromopropyl)carbamateHCID 118522397N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide

生成物 1

HCID 118522579[3-(4-{3-(5-Chloro-2-difluoromethoxyphenyl)-4-[(pyrazolo[1,5-a]pyrimidine-3-carbonyl)amino]pyrazol-1-yl}piperidin-1-yl)propyl]carbamic acid tert-butyl ester収率 101.5%

試薬・触媒・溶媒

2
HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

A mixture of pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [3-(5-chloro-2-difluoromethoxyphenyl)-1-piperidin-4-yl-1H-pyrazol-4-yl]amide (100 mg, 0.20 mmol), (3-bromo-propyl)-carbamic acid tert-butyl ester (71 mg, 0.3 mmol) and potassium carbonate (45 mg, 0.32 mmol) in DMF (2 mL) was heated at 60° C. for 1.5 hours. The reaction mixture was allowed to cool to ambient temperature, diluted with water and extracted with dichloromethane. The organic layer was separated, washed with brine, dried (Na2SO4) and evaporated. The resultant residue was chromatographed on silica eluting with dichloromethane on a gradient of 2M ammonia in methanol (0-6%) to give [3-(4-{3-(5-chloro-2-difluoromethoxyphenyl)-4-[(pyrazolo[1,5-a]pyrimidine-3-carbonyl)amino]pyrazol-1-yl}piperidin-1-yl)propyl]carbamic acid tert-butyl ester as a yellow oil (131 mg, 100%). LCMS (Method 4) [M+H]+=675.0, RT=2.86 min.

後処理

  1. temperatureto cool to ambient temperature
  2. extractionextracted with dichloromethane
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried (Na2SO4)
  6. customevaporated
  7. customThe resultant residue was chromatographed on silica eluting with dichloromethane on a gradient of 2M ammonia in methanol (0-6%)

出典と根拠

ORDレコード
ord-ddf9d944f2e2449098957401d9d2f514
出典データセット
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09346815B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート