Methanol → N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-5-(4-chlorophenylsulfanyl)-thiophene-2-carboxamide

HRID 1359636노트

반응식

HRID 1359636 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[S:13][C:12]([C:14]([OH:16])=O)=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.C1(OP(Cl)(OC2C=CC=CC=2)=O)C=CC=CC=1.[NH2:34][C@@H:35]1[CH:40]2[CH2:41][CH2:42][N:37]([CH2:38][CH2:39]2)[CH2:36]1.CO>C(Cl)Cl>[N:37]12[CH2:42][CH2:41][CH:40]([CH2:39][CH2:38]1)[C@@H:35]([NH:34][C:14]([C:12]1[S:13][C:9]([S:8][C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)=[CH:10][CH:11]=1)=[O:16])[CH2:36]2

참가 물질

6

반응물 4

HCID 887MethanolHCID 75654Diphenyl chlorophosphateHCID 719215(3R)-1-Azabicyclo(2.2.2)octan-3-amineHCID 223504025-(4-Chlorophenylthio)thiophene-2-carboxylic acid

생성물 1

HCID 9969948N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-5-(4-chlorophenylsulfanyl)-thiophene-2-carboxamide수율 71%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

TEA (1.5 mL, 10.9 mmol) was added to a suspension of the product of Step 33b (2.7 g, 10 mmol) in CH2Cl2 (100 mL). Diphenylchlorophosphate (2.08 mL, 10 mmol) was added and the resulting solution is stirred at room temperature for 30 minutes. To this solution is added a solution of (R)-3-aminoquinuclidine (1M in DMF, 9.1 mL, 9.1 mmol). The resulting solution is stirred overnight at room temperature. MeOH is added and the mixture is poured through a column of AG50Wx2 ion exchange resin (H+form). The resin is washed with MeOH, then the product is eluted with 5% TEA in MeOH. The eluent is evaporated to dryness and the resulting solid is triturated with ether and dried in vacuo to yield the desired product (2.4 g, 71%). Alternatively, these compounds can be converted to their hydrochloride salts and crystallized from MeOH/IPA. MS for C18H19ClN2OS2 (ESI) (M+H)+ m/z 379.

후처리

  1. stirringThe resulting solution is stirred overnight at room temperature
  2. additionthe mixture is poured through a column of AG50Wx2 ion exchange resin (H+form)
  3. washThe resin is washed with MeOH
  4. washthe product is eluted with 5% TEA in MeOH
  5. customThe eluent is evaporated to dryness
  6. customthe resulting solid is triturated with ether
  7. customdried in vacuo

출처 및 근거

ORD 기록
ord-eda70498ad694efbb6c24bd352771331
출처 데이터셋
uspto-grants-2003_07
특허 번호
US06599916B2

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