Cesium carbonate → tert-Butyl 9-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-6-methyl-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate

HRID 626819ノート

反応式

HRID 626819 の反応式
C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:7][C:8]1[C:16]2[C:11](=[N:12][CH:13]=[N:14][C:15]=2[NH2:17])[NH:10][N:9]=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:38](Cl)[CH3:39])[C:22]2[O:28][CH2:27][CH2:26][N:25]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:24][C:23]=2[C:36]=1[CH3:37]>CN(C)C=O.C(OCC)(=O)C>[NH2:17][C:15]1[N:14]=[CH:13][N:12]=[C:11]2[N:10]([CH:38]([C:21]3[C:22]4[O:28][CH2:27][CH2:26][N:25]([C:29]([O:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[O:30])[CH2:24][C:23]=4[C:36]([CH3:37])=[C:19]([Cl:18])[CH:20]=3)[CH3:39])[N:9]=[C:8]([CH3:7])[C:16]=12

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 86697516tert-Butyl 7-chloro-9-(1-chloroethyl)-6-methyl-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylateHCID 178434474HCID 178434474、化合物

生成物 1

HCID 71765363tert-Butyl 9-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-7-chloro-6-methyl-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate収率 62%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

Cesium carbonate (500 mg, 2 mmol) was added to a mixture of 3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (150 mg, 0.98 mmol) in N,N-dimethylformamide (30 mL) and stirred for 10 minutes. To this was added tert-butyl 7-chloro-9-(1-chloroethyl)-6-methyl-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (290 mg, 0.82 mmol) in N,N-dimethylformamide (1 mL) and the reaction was stirred at 80° C. for 1 hour. The mixture was diluted with ethyl acetate and washed with water and brine. The extracts were dried over sodium sulfate, filtered and evaporated. The crude was dissolved in methylene chloride and filtered to remove insoluble material (unwanted regioisomer). Purification on silica gel using ethyl acetate in hexanes (0-100%) followed by methanol in ethyl acetate (0-15%) gave the desired compound (240 mg, 62%). LCMS calculated for C23H30ClN6O3(M+H)+: m/z=473.2; found: 473.2. 1H NMR (300 MHz, CD3OD): δ 8.14 (s, 1 H), 7.29 (m, 1 H), 6.32 (m, 1 H), 4.70 (m, 1 H), 4.40 (m, 1 H), 3.83 (m, 2 H), 3.57 (m, 2 H), 2.58 (s, 3 H), 2.48 (m, 3 H), 1.78 (m, 3 H), 1.39 (, 9H).

後処理

  1. stirringthe reaction was stirred at 80° C. for 1 hour
  2. washwashed with water and brine
  3. dry with materialThe extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. dissolutionThe crude was dissolved in methylene chloride
  7. filtrationfiltered
  8. customto remove insoluble material (unwanted regioisomer)
  9. customPurification on silica gel

出典と根拠

ORDレコード
ord-1ee163424a8744b899a2713f3180e47d
出典データセット
uspto-grants-2016_04
特許番号
US09309251B2

反応ノート

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