Trifluoroacetic acid → 7-chloro-6-[2-(cyclopropylmethyl-amino)-thiazol-5-ylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 1670568노트

반응식

HRID 1670568 반응식
C(OC([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([CH2:20][S:21][C:22]3[S:26][C:25]([NH:27][CH2:28][CH:29]4[CH2:31][CH2:30]4)=[N:24][CH:23]=3)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[Cl:19][C:16]1[CH:17]=[CH:18][C:11]2[CH2:10][CH2:9][NH:8][CH2:14][CH2:13][C:12]=2[C:15]=1[CH2:20][S:21][C:22]1[S:26][C:25]([NH:27][CH2:28][CH:29]2[CH2:31][CH2:30]2)=[N:24][CH:23]=1

참가 물질

4

반응물 2

HCID 6422Trifluoroacetic acidHCID 866237063-tert-butoxycarbonyl-7-chloro-6-[2-(cyclopropylmethyl-amino)-thiazol-5-ylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine

생성물 1

HCID 598222607-chloro-6-[2-(cyclopropylmethyl-amino)-thiazol-5-ylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine수율 83.3%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of 3-tert-butoxycarbonyl-7-chloro-6-[2-(cyclopropylmethyl-amino)-thiazol-5-ylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.113 g, 0.237 mmol) in anhydrous DCM (4.9 mL) at room temperature add trifluoroacetic acid (4.9 mL) and stir the solution at room temperature overnight. Concentrate in vacuo and elute the residue through a SCX column (20 g). Dissolve the residue in DCM, load the solution on to an Analogix® column (40 g) and purify the crude mixture by preparative liquid chromatography (100:0 to 90:10 DCM/2M ammonia in methanol over 30 min; 90:10 DCM/2M ammonia in methanol over 33 min; 35 mL/min) to afford 7-chloro-6-[2-(cyclopropylmethyl-amino)-thiazol-5-ylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.075 g, 83%). MS (ES+) m/z: 380.1 (M+H)+.

후처리

  1. concentrationConcentrate in vacuo
  2. washelute the residue through a SCX column (20 g)
  3. dissolutionDissolve the residue in DCM
  4. customload the solution on to an Analogix® column (40 g) and purify the crude mixture by preparative liquid chromatography (100:0 to 90:10 DCM/2M ammonia in methanol over 30 min; 90:10 DCM/2M ammonia in methanol over 33 min; 35 mL/min)

출처 및 근거

ORD 기록
ord-616abb5ae80742fd8c2800b259bd35c2
출처 데이터셋
uspto-grants-2011_08
특허 번호
US07994163B2

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