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

HRID 1670577Notes

Reaction equation

HRID 1670577 reaction equation
C(OC([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([CH2:20][S:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]4[N:29]=[C:30]([NH:33][CH2:34][CH:35]5[CH2:37][CH2:36]5)[S:31][CH:32]=4)=[CH: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[CH:23]=[CH:24][C:25]([C:28]2[N:29]=[C:30]([NH:33][CH2:34][CH:35]3[CH2:37][CH2:36]3)[S:31][CH:32]=2)=[CH:26][CH:27]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 866237093-tert-butoxycarbonyl-7-chloro-6-{4-[2-(cyclopropylmethyl-amino)-thiazol-4-yl]-phenylthiomethyl}-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 598222837-chloro-6-{4-[2-(cyclopropylmethyl-amino)-thiazol-4-yl]-phenylthiomethyl}-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-tert-butoxycarbonyl-7-chloro-6-{4-[2-(cyclopropylmethyl-amino)-thiazol-4-yl]-phenylthiomethyl}-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.305 g, 0.548 mmol) in dry DCM (12.6 mL) at room temperature add trifluoroacetic acid (12.6 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 (40 g) and purify the crude mixture by preparative liquid chromatography (100:0 to 95:5 DCM/2M ammonia in methanol over 33 min; 95:5 to 90:10 DCM/2M ammonia in methanol over 33 min; 35 mL/min) to afford 7-chloro-6-{4-[2-(cyclopropylmethyl-amino)-thiazol-4-yl]-phenylthiomethyl}-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.215 g, 86%) as an off-white foam.

Workup

  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 a RediSep® column (40 g) and purify the crude mixture by preparative liquid chromatography (100:0 to 95:5 DCM/2M ammonia in methanol over 33 min; 95:5 to 90:10 DCM/2M ammonia in methanol over 33 min; 35 mL/min)

Sources & evidence

ORD record
ord-4982451f7ceb4069906603d0d90a3ff8
Source dataset
uspto-grants-2011_08
Patent number
US07994163B2

Reaction notes

Loading…