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

HRID 1670565노트

반응식

HRID 1670565 반응식
C(OC([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([CH2:20][S:21][C:22]3[S:23][C:24]([NH:27][CH2:28][CH:29]4[CH2:31][CH2:30]4)=[N:25][N:26]=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:23][C:24]([NH:27][CH2:28][CH:29]2[CH2:31][CH2:30]2)=[N:25][N:26]=1

참가 물질

4

반응물 2

HCID 6422Trifluoroacetic acidHCID 598223173-tert-Butoxycarbonyl-7-chloro-6-[5-(cyclopropylmethyl-amino)-[1,3,4]thiadiazol-2-ylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine

생성물 1

HCID 598223037-chloro-6-[5-(cyclopropylmethyl-amino)-[1,3,4]thiadiazol-2-ylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine수율 78.3%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of 3-tert-butoxycarbonyl-7-chloro-6-[5-(cyclopropylmethyl-amino)-[1,3,4]thiadiazol-2-ylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.082 g, 0.171 mmol) in anhydrous DCM (3.5 mL) at room temperature add trifluoroacetic acid (3.5 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 a RediSep® column (12 g) and purify the crude mixture by preparative liquid chromatography (100:0 to 90:10 DCM/2M ammonia in methanol over 33 min; 35 mL/min) to afford 7-chloro-6-[5-(cyclopropylmethyl-amino)-[1,3,4]thiadiazol-2-ylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.051 g, 78%). MS (ES+) m/z: 381.1 (M+H)+. To a solution of 7-chloro-6-[5-(cyclopropylmethyl-amino)-[1,3,4]thiadiazol-2-ylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.044 g, 0.116 mmol) in absolute ethanol (5 mL), add succinic acid (0.014 g, 0.116 mmol). After acid dissolves, concentrate the reaction mixture in vacuo. Combine the residue with MTBE, concentrate in vacuo several times and dry under high vacuum at room temperature overnight to obtain the title compound (0.058 g, 100%) as a white foam. MS (ES+) m/z: 381.0 (M+H)+.

후처리

  1. concentrationConcentrate in
  2. washvacuo and elute the residue through a SCX column (20 g)
  3. dissolutionDissolve the residue in DCM
  4. customload the solution on to a RediSep® column (12 g) and purify the crude mixture by preparative liquid chromatography (100:0 to 90:10 DCM/2M ammonia in methanol over 33 min; 35 mL/min)

출처 및 근거

ORD 기록
ord-2442853ba17b4dfdbbdc89ff9d01db3a
출처 데이터셋
uspto-grants-2011_08
특허 번호
US07994163B2

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