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

HRID 1670565ノート

反応式

HRID 1670565 の反応式
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

参加物

4

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-2442853ba17b4dfdbbdc89ff9d01db3a
出典データセット
uspto-grants-2011_08
特許番号
US07994163B2

反応ノート

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