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 626819노트

반응식

HRID 626819 반응식
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

참가 물질

6

반응물 3

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

생성물 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)-carboxylate수율 62%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매2회HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-1ee163424a8744b899a2713f3180e47d
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309251B2

반응 노트

불러오는 중…