N-bromobutanimide → 2-Propen-1-yl (3-{5-(2-chloro-4-pyrimidinyl)-2-[1-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-1-methylethyl]-1,3-thiazol-4-yl}-2-fluorophenyl)carbamate

HRID 1962065Notes

Reaction equation

HRID 1962065 reaction equation
BrN1C(=O)CCC1=O.[Cl:9][C:10]1[N:15]=[C:14]([CH2:16][C:17]([C:19]2[C:20]([F:32])=[C:21]([NH:25][C:26](=[O:31])[O:27][CH2:28][CH:29]=[CH2:30])[CH:22]=[CH:23][CH:24]=2)=O)[CH:13]=[CH:12][N:11]=1.[NH2:33][C:34](=[S:46])[C:35]([NH:38][C:39](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:37])[CH3:36]>ClCCl.CCOC(C)=O>[Cl:9][C:10]1[N:15]=[C:14]([C:16]2[S:46][C:34]([C:35]([NH:38][C:39]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:45])([CH3:37])[CH3:36])=[N:33][C:17]=2[C:19]2[C:20]([F:32])=[C:21]([NH:25][C:26](=[O:31])[O:27][CH2:28][CH:29]=[CH2:30])[CH:22]=[CH:23][CH:24]=2)[CH:13]=[CH:12][N:11]=1

Participants

6

Reactant 3

HCID 67184N-bromobutanimideHCID 15186362Carbamic acid, (2-amino-1,1-dimethyl-2-thioxoethyl)-, 1,1-dimethylethyl esterHCID 579899922-Propen-1-yl {3-[(2-chloro-4-pyrimidinyl)acetyl]-2-fluorophenyl}carbamate

Product 1

HCID 579897572-Propen-1-yl (3-{5-(2-chloro-4-pyrimidinyl)-2-[1-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-1-methylethyl]-1,3-thiazol-4-yl}-2-fluorophenyl)carbamateYield 54.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

N-Bromosuccinimide (0.763 g, 4.29 mmol) was added to a solution of 2-propen-1-yl {3-[(2-chloro-4-pyrimidinyl)acetyl]-2-fluorophenyl}carbamate (1.5 g, 4.29 mmol) in dichloromethane (DCM) (50 mL). After 1 h of stirring, 1,1-dimethylethyl (2-amino-1,1-dimethyl-2-thioxoethyl)carbamate (0.936 g, 4.29 mmol) was added to the reaction mixture and heated to 80° C. for 2 h. The reaction mixture was diluted with 150 cc of EtOAc and washed with water (5×100 cc). The EtOAc layer was dried over MgSO4 and filtered and concentrated in vacuo. The residue was purified via chromatography on silica gel using Hex to 25% EtOAc in Hex to obtain the title compound (1.28 g, 54% yield). MS (ESI): 548.3 [M+H]+

Workup

  1. washwashed with water (5×100 cc)
  2. dry with materialThe EtOAc layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified via chromatography on silica gel using Hex to 25% EtOAc in Hex

Sources & evidence

ORD record
ord-9188908219f243ea92404a09243aefc0
Source dataset
uspto-grants-2013_04
Patent number
US08415345B2

Reaction notes

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