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

HRID 529487Notes

Reaction equation

HRID 529487 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].[S:33]1[CH:37]=[CH:36][N:35]=[C:34]1[NH2:38].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]([CH3:11])([CH3:12])[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:38][C:34]3[S:33][CH:37]=[CH:36][N:35]=3)[N:20]12

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 21552-AminothiazoleHCID 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 86706202tert-butyl (4S,7S,10aS)-5-oxo-7-(thiazol-2-ylcarbamoyl)octahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamateYield 51.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

DIPEA (0.036 mL, 0.21 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 (55 mg, 0.16 mmol), thiazol-2-amine (19.2 mg, 0.192 mmol) and 1-hydroxy-7-azabenzotriazole (26.1 mg, 0.192 mmol) in DMF (0.6 mL). Then EDC (36.7 mg, 0.192 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-(thiazol-2-ylcarbamoyl)octahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate (35 mg, 0.082 mmol, 51% yield) as a white solid. Anal. Calcd. for C18H26N4O4S2 m/z 426.5. found: 427.1 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 7.45 (s, 1H), 6.98 (s, 1H), 5.96 (m, 1H), 5.37 (br s, 1H), 5.28 (br s, 1H), 3.35 (m, 2H), 2.94 (m, 2H), 2.36 (m, 1H), 2.45 (m, 1H), 2.05 (m, 2H), 1.53-1.50 (m, 4H), 1.50 (s, 9H).

Workup

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

Sources & evidence

ORD record
ord-c30b2a27b4be4a58a27855d312122fc2
Source dataset
uspto-grants-2016_05
Patent number
US09346852B2

Reaction notes

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