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

HRID 1670580Notes

Reaction equation

HRID 1670580 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][N: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:27]=[CH:26][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:24][N:23]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 866237113-tert-butoxycarbonyl-7-chloro-6-{5-[2-(cyclopropylmethyl-amino)-thiazol-4-yl]-pyridin-2-ylthiomethyl}-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 598222797-chloro-6-{5-[2-(cyclopropylmethyl-amino)-thiazol-4-yl]-pyridin-2-ylthiomethyl}-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 99.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-tert-butoxycarbonyl-7-chloro-6-{5-[2-(cyclopropylmethyl-amino)-thiazol-4-yl]-pyridin-2-ylthiomethyl}-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.386 g, 0.693 mmol) in anhydrous DCM (16 mL) at room temperature add trifluoroacetic acid (15.9 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 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-{5-[2-(cyclopropylmethyl-amino)-thiazol-4-yl]-pyridin-2-ylthiomethyl}-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.315 g, 99%). MS (ES+) m/z: 457.1 (M+H)+.

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-768572c7dde84e0e893489ad7da02738
Source dataset
uspto-grants-2011_08
Patent number
US07994163B2

Reaction notes

Loading…