1,2-Dichloroethane → tert-butyl (4S,7S,10aS)-5-oxo-7-(propylcarbamoyl)octahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate

HRID 529489Notes

Reaction equation

HRID 529489 reaction equation
CCN(C(C)C)C(C)C.[C:10]([O:14][C:15]([NH:17][C@H:18]1[CH2:24][CH2:23][S:22][C@H:21]2[CH2:25][CH2:26][CH2:27][C@@H:28]([C:29](O)=[O:30])[N:20]2[C:19]1=[O:32])=[O:16])([CH3:13])([CH3:12])[CH3:11].[CH2:33]([NH2:36])[CH2:34][CH3:35].ON1C2N=CC=CC=2N=N1.C(Cl)CCl>CN(C=O)C>[O:32]=[C:19]1[C@@H:18]([NH:17][C:15](=[O:16])[O:14][C:10]([CH3:12])([CH3:11])[CH3:13])[CH2:24][CH2:23][S:22][C@H:21]2[CH2:25][CH2:26][CH2:27][C@@H:28]([C:29](=[O:30])[NH:36][CH2:33][CH2:34][CH3:35])[N:20]12

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 7852PropylamineHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 68292173(4S,7S,10aS)-4-(tert-butoxycarbonylamino)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepine-7-carboxylic acid

Product 1

HCID 86706205tert-butyl (4S,7S,10aS)-5-oxo-7-(propylcarbamoyl)octahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamateYield 100%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

DIPEA (0.033 mL, 0.19 mmol) was added to a cold (0° C.) mixture of (4S,7S,10aS)-4-(tert-butoxycarbonylamino)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepine-7-carboxylic acid (50 mg, 0.15 mmol), propan-1-amine (10.3 mg, 0.174 mmol) and 1-hydroxy-7-azabenzotriazole (23.7 mg, 0.174 mmol) in DMF (0.3 mL). Then, EDC (33.4 mg, 0.174 mmol) was added. The reaction was stirred at rt for 8 hr. The crude mixture was purified by RP prep-HPLC (Method B) to give tert-butyl (4S,7S,10aS)-5-oxo-7-(propylcarbamoyl)octahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate (56 mg, 0.15 mmol, 100% yield) as a white solid. Anal. Calcd. for C18H31N3O4S m/z 385.5. found: 386.2 (M+H)+. 1H NMR (400 MHz, CDCl3) δ ppm 6.02 (br s, 1H), 5.27 (br s, 1H), 5.02 (br s, 1H), 4.77 (m, 1H), 3.23 (m, 2H), 2.89 (m, 1H), 2.36 (m, 1H), 2.41 (m, 2H), 2.05 (m, 2H), 1.53-1.50 (m, 6H), 1.50 (s, 9H), 0.90 (t, J=7.5 Hz, 3H).

Workup

  1. customThe crude mixture was purified by RP prep-HPLC (Method B)

Sources & evidence

ORD record
ord-00683b47361f44ca8d9b1389f50f1fc6
Source dataset
uspto-grants-2016_05
Patent number
US09346852B2

Reaction notes

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