(Diethylamino)sulfur trifluoride → (+/-)-10-[Fluoro-(4-fluoro-2-methoxy-phenyl)-methyl]-2-pyrimidin-4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-a]azepin-4-one

HRID 1520421Notes

Reaction equation

HRID 1520421 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](O)[CH:9]2[CH2:15][CH2:14][CH2:13][CH2:12][N:11]3[C:16](=[O:26])[CH:17]=[C:18]([C:20]4[CH:25]=[CH:24][N:23]=[CH:22][N:21]=4)[N:19]=[C:10]23)=[C:4]([O:28][CH3:29])[CH:3]=1.C(N(S(F)(F)[F:36])CC)C>ClCCl>[F:36][CH:8]([C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=1[O:28][CH3:29])[CH:9]1[CH2:15][CH2:14][CH2:13][CH2:12][N:11]2[C:16](=[O:26])[CH:17]=[C:18]([C:20]3[CH:25]=[CH:24][N:23]=[CH:22][N:21]=3)[N:19]=[C:10]12

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 44600980(+/-)-10-[(4-Fluoro-2-methoxy-phenyl)-hydroxy-methyl]-2-pyrimidin-4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-a]azepin-4-one

Product 1

HCID 44600982(+/-)-10-[Fluoro-(4-fluoro-2-methoxy-phenyl)-methyl]-2-pyrimidin-4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-a]azepin-4-oneYield 25%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 0.290 g (0.73 mmol) of (+/−)-10-[(4-fluoro-2-methoxy-phenyl)-hydroxy-methyl]-2-pyrimidin-4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-α]azepin-4-one (example 4) in dichloromethane (14 mL) under argon at −78° C. was added 0.294 g of diethylaminosulfur trifluoride (1.83 mmol) diluted in 5 ml of dichloromethane. The reaction was allowed to increase to room temperature. The reaction was stirred at room temperature for 2 h; the mixture was quenched at 0° C. with the addition of methanol and stirred overnight. A saturated solution of ammonium chloride was added and the mixture was extracted with dichloromethane. The organic phase was washed with a saturated solution of sodium chloride and dried over sodium sulfate and concentrated. The residue was purified by flash chromatography (dichloromethane with 2% of methanol and 0.2% of ammonia) to afford 0.072 g (25%) of a white solid as an isomer mixture (95/5).

Workup

  1. customthe mixture was quenched at 0° C. with the addition of methanol
  2. stirringstirred overnight
  3. additionA saturated solution of ammonium chloride was added
  4. extractionthe mixture was extracted with dichloromethane
  5. washThe organic phase was washed with a saturated solution of sodium chloride
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography (dichloromethane with 2% of methanol and 0.2% of ammonia)

Sources & evidence

ORD record
ord-0a3a54ae983d49d4a16251f67f9bb6a1
Source dataset
uspto-grants-2015_07
Patent number
US09073914B2

Reaction notes

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