Water → tert-butyl (S)-1-(5-(3-cyano-4-fluorophenyl)thiazol-2-ylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

HRID 2109713Notes

Reaction equation

HRID 2109713 reaction equation
Br[C:2]1[S:6][C:5]([N:7](C(OC(C)(C)C)=O)[CH2:8][C@@H:9]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)=[N:4][CH:3]=1.[F:36][C:37]1[CH:44]=[CH:43][C:42](B2OC(C)(C)C(C)(C)O2)=[CH:41][C:38]=1[C:39]#[N:40].C(=O)([O-])[O-].[Na+].[Na+].O>O1CCOCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:39]([C:38]1[CH:41]=[C:42]([C:2]2[S:6][C:5]([NH:7][CH2:8][C@@H:9]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:26])([CH3:25])[CH3:27])[CH2:10][C:11]3[CH:12]=[CH:13][C:14]([C:17]([F:18])([F:19])[F:20])=[CH:15][CH:16]=3)=[N:4][CH:3]=2)[CH:43]=[CH:44][C:37]=1[F:36])#[N:40]

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 114023612-Fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrileHCID 57634226(S)-tert-butyl 1-(N-(5-bromothiazol-2-yl)-tert-butoxylcarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

Product 1

HCID 86613766tert-butyl (S)-1-(5-(3-cyano-4-fluorophenyl)thiazol-2-ylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of (S)-tert-butyl 1-(N-(5-bromothiazol-2-yl)-tert-butoxylcarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate (0.20 g, 0.34 mmol) in 3 mL of dioxane in a microwave safe tube, was added 2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (0.13 g, 0.52 mmol), sodium carbonate, 2 M in water (0.69 mL, 1.4 mmol), and tetrakis(triphenylphosphine) palladium (0.020 g, 0.017 mmol). The mixture was purged with nitrogen for 30 seconds and the tube was sealed. The tube was then heated to 120° C. in a Personal Chemistry microwave unit for 20 minutes. The mixture was diluted with 5 mL of water and extracted twice with 8 mL of EtOAc. The combined organic extracts were washed with 7 mL of brine and dried over MgSO4. Filtration and concentration under reduced pressure afforded tert-butyl (S)-1-(5-(3-cyano-4-fluorophenyl)thiazol-2-ylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate, mixed with the other two products. The crude mixture was carried on to the next reaction without any further purification.

Workup

  1. customThe mixture was purged with nitrogen for 30 seconds
  2. customthe tube was sealed
  3. additionThe mixture was diluted with 5 mL of water
  4. extractionextracted twice with 8 mL of EtOAc
  5. washThe combined organic extracts were washed with 7 mL of brine
  6. dry with materialdried over MgSO4
  7. filtrationFiltration and concentration under reduced pressure

Sources & evidence

ORD record
ord-bedf2753ccb0441faddee8cc132e3581
Source dataset
uspto-grants-2009_04
Patent number
US07514566B2

Reaction notes

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