N-bromobutanimide → 1,1-Dimethylethyl 4-[5-(2-chloro-4-pyrimidinyl)-4-(2-fluoro-3-{[(2-propen-1-yloxy)carbonyl]amino}phenyl)-1,3-thiazol-2-yl]-4-methyl-1-piperidinecarboxylate

HRID 239581Notes

Reaction equation

HRID 239581 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][C:9]([C:11]2[C:12]([F:24])=[C:13]([NH:17][C:18](=[O:23])[O:19][CH2:20][CH:21]=[CH2:22])[CH:14]=[CH:15][CH:16]=2)=O)[CH:5]=[CH:4][N:3]=1.C1C(=O)N(Br)C(=O)C1.[NH2:33][C:34]([C:36]1([CH3:49])[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH2:37]1)=[S:35]>CN(C)C(=O)C>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:35][C:34]([C:36]3([CH3:49])[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH2:37]3)=[N:33][C:9]=2[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([NH:17][C:18]([O:19][CH2:20][CH:21]=[CH2:22])=[O:23])[C:12]=2[F:24])[CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 67184N-bromobutanimideHCID 57473378HCID 57473378, compoundHCID 579899922-Propen-1-yl {3-[(2-chloro-4-pyrimidinyl)acetyl]-2-fluorophenyl}carbamate

Product 1

HCID 579898811,1-Dimethylethyl 4-[5-(2-chloro-4-pyrimidinyl)-4-(2-fluoro-3-{[(2-propen-1-yloxy)carbonyl]amino}phenyl)-1,3-thiazol-2-yl]-4-methyl-1-piperidinecarboxylateYield 54%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2-propen-1-yl {3-[(2-chloro-4-pyrimidinyl)acetyl]-2-fluorophenyl}carbamate (0.738 g, 2.110 mmol) in N,N-dimethylacetamide (8 mL) was added NBS (0.376 g, 2.110 mmol), and the reaction mixture was stirred for 1.5 h. 1,1-Dimethylethyl 4-(aminocarbonothioyl)-4-methyl-1-piperidinecarboxylate (0.545 g, 2.110 mmol) was added and the mixture was heated to 80° C. for 30 min. The reaction mixture was cooled, quenched with water (20 mL), and extracted with EtOAc (3×). The extract was dried over Na2SO4, filtered and concentrated. The residue was purified using column chromatography (hexane/EtOAc, 0 to 100%) to obtain the title compound (670 mg). MS (ESI): 588.2 [M+1]+.

Workup

  1. temperatureThe reaction mixture was cooled
  2. customquenched with water (20 mL)
  3. extractionextracted with EtOAc (3×)
  4. dry with materialThe extract was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified

Sources & evidence

ORD record
ord-6eb06f6fb1ac495da8c2d7ee6d8e6bbf
Source dataset
uspto-grants-2014_02
Patent number
US08642759B2

Reaction notes

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