Cesium carbonate → 6-fluoro-3-(4-{4-[(2-methylpyridin-3-yl)oxy]phenyl}-1H-1,2,3-triazol-1-yl)-1-(2,2,2-trifluoroethyl)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one

HRID 2035718Notes

Reaction equation

HRID 2035718 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[N:10][N:11]([CH:13]3[CH2:19][CH2:18][C:17]4[C:20]([F:24])=[CH:21][CH:22]=[CH:23][C:16]=4[N:15]([CH2:25][C:26]([F:29])([F:28])[F:27])[C:14]3=[O:30])[CH:12]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[OH:37][C:38]1[C:39]([CH3:44])=[N:40][CH:41]=[CH:42][CH:43]=1.CC(C)(C(=O)CC(=O)C(C)(C)C)C>CN1C(=O)CCC1.CCOC(C)=O.O>[F:24][C:20]1[C:17]2[CH2:18][CH2:19][CH:13]([N:11]3[CH:12]=[C:8]([C:5]4[CH:6]=[CH:7][C:2]([O:37][C:38]5[C:39]([CH3:44])=[N:40][CH:41]=[CH:42][CH:43]=5)=[CH:3][CH:4]=4)[N:9]=[N:10]3)[C:14](=[O:30])[N:15]([CH2:25][C:26]([F:29])([F:28])[F:27])[C:16]=2[CH:23]=[CH:22][CH:21]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 707192-Methylpyridin-3-olHCID 580635063-[4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl]-6-fluoro-1-(2,2,2-trifluoroethyl)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one

Product 1

HCID 468417266-fluoro-3-(4-{4-[(2-methylpyridin-3-yl)oxy]phenyl}-1H-1,2,3-triazol-1-yl)-1-(2,2,2-trifluoroethyl)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

3-[4-(4-Bromophenyl)-1H-1,2,3-triazol-1-yl]-6-fluoro-1-(2,2,2-trifluoroethyl)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one (150 mg, 0.310 mmol), cesium carbonate (202 mg, 0.621 mmol), 3-hydroxy-2-methylpyridine (67.7 mg, 0.621 mmol), cuprous chloride (915.36 mg, 0.155 mmol), 2,2,6,6-tetramethyl-3,5-heptanedione (14.30 mg, 0.078 mmol) in NMP (1.55 mL) in a sealed microwave vial was heated to 120° C. overnight in an oil bath. The reaction vessel was allowed to cool before water was added to dilute the mixture; EtOAc was then added to extract the product. The organic phase was separated and washed with water (2×) and brine (1×) before being dried with Na2SO4 and evaporated to afford an oil. This material was chromatographed on silica (0-80% EtOAc in hexanes to yield 68.4 mg as a solid.

Workup

  1. additionwas added
  2. additionto dilute the mixture
  3. extractionto extract the product
  4. customThe organic phase was separated
  5. washwashed with water (2×) and brine (1×)
  6. dry with materialbefore being dried with Na2SO4
  7. customevaporated
  8. customto afford an oil
  9. customThis material was chromatographed on silica (0-80% EtOAc in hexanes
  10. customto yield 68.4 mg as a solid

Sources & evidence

ORD record
ord-0fbcc59d5f774c6f9e4c55e1bd9bbe9c
Source dataset
uspto-grants-2013_11
Patent number
US08575150B2

Reaction notes

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