Hydrochloric Acid → N-[2-(1,1-Dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]prolinamide

HRID 540133Notes

Reaction equation

HRID 540133 reaction equation
[O:1]=[S:2]1(=[O:39])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[CH2:6][N:5]([C:13]2[CH:22]=[C:21]([NH:23][C:24]([CH:26]3[CH2:30][CH2:29][CH2:28][N:27]3C(OC(C)(C)C)=O)=[O:25])[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([CH3:38])[CH:19]=3)[N:14]=2)[CH2:4][CH2:3]1.Cl>C(OCC)(=O)C>[O:39]=[S:2]1(=[O:1])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[CH2:6][N:5]([C:13]2[CH:22]=[C:21]([NH:23][C:24](=[O:25])[C@@H:26]3[CH2:30][CH2:29][CH2:28][NH:27]3)[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([CH3:38])[CH:19]=3)[N:14]=2)[CH2:4][CH2:3]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 71255504tert-Butyl 2-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]carbamoyl}pyrrolidine-1-carboxylate

Product 1

HCID 71255385N-[2-(1,1-Dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]prolinamideYield 52.9%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of tert-butyl 2-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]carbamoyl}pyrrolidine-1-carboxylate (250 mg, 0.44 mmol) in ethyl acetate (5 mL) was added a solution of hydrochloride in ethyl acetate (4 N, 20 mL) dropwise in an ice-water bath. After being stirred at room temperature for 14 hours, the reaction mixture was concentrated in vacuo. The residue was purified by preparative TLC to give 104.8 mg of the desired product (yield was 48%). MS obsd. (ESI+) [(M+H)+] 451, 1H NMR (400 MHz, DMSO-d6) δ ppm 7.96 (s, 1 H), 7.88-7.84 (m, 2 H), 7.63-7.59 (m, 1 H), 7.54 (s, 1 H) 7.49-7.44 (m, 2 H), 7.39-7.37 (m, 2 H), 7.00 (s, 1 H), 5.04 (s, 2 H), 4.40 (s, 2 H), 4.16-4.12 (t, J=5.2 Hz, 1 H), 3.64 (s, 2 H) 3.15-3.01 (m, 3 H), 2.39 (s, 3 H), 2.23-2.20 (m, 1 H), 1.95-1.90 (m, 1 H), 1.80-1.75 (m, 1 H).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. customThe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-42cb9275265948f6abf0edd52a0286ec
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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