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

HRID 1670568ノート

反応式

HRID 1670568 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: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

参加物

4

反応物 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

生成物 1

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

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-[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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-616abb5ae80742fd8c2800b259bd35c2
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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