Phosphorus oxide (P4O10) → HCID 67433841, compound

HRID 1040211Notes

Reaction equation

HRID 1040211 reaction equation
O[C:2]1([C:10]2[S:11][C:12]([C:15]3[CH:20]=[C:19]([NH:21][C:22]4[N:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][N:23]=4)[CH:18]=[C:17]([CH3:32])[CH:16]=3)=[CH:13][N:14]=2)[CH2:8][CH2:7][NH:6][C:5](=[O:9])[CH2:4][CH2:3]1.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[C:47](=[O:50])(O)[O-:48].[Na+]>O>[F:29][C:28]([F:31])([F:30])[C:47]([OH:48])=[O:50].[CH3:32][C:17]1[CH:16]=[C:15]([C:12]2[S:11][C:10]([C:2]3[CH2:8][CH2:7][NH:6][C:5](=[O:9])[CH2:4][CH:3]=3)=[N:14][CH:13]=2)[CH:20]=[C:19]([NH:21][C:22]2[N:27]=[C:26]([C:28]([F:30])([F:31])[F:29])[CH:25]=[CH:24][N:23]=2)[CH:18]=1.[CH3:32][C:17]1[CH:16]=[C:15]([C:12]2[S:11][C:10]([C:2]3[CH2:3][CH2:4][C:5](=[O:9])[NH:6][CH2:7][CH:8]=3)=[N:14][CH:13]=2)[CH:20]=[C:19]([NH:21][C:22]2[N:27]=[C:26]([C:28]([F:30])([F:31])[F:29])[CH:25]=[CH:24][N:23]=2)[CH:18]=1

Participants

7

Reactant 3

HCID 14812Phosphorus oxide (P4O10)HCID 516892Sodium BicarbonateHCID 53251351HCID 53251351, compound

Product 3

HCID 6422Trifluoroacetic acidYield 0.1%HCID 67258761HCID 67258761, compoundHCID 67433841HCID 67433841, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
65 °C

Procedure

5-Hydroxy-5-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]azepan-2-one (Example 10, 300 mg, 0.65 mmol) was suspended neat in phosphorus pentoxide (1.2 mL, 12.9 mmol) and stirred at 65° C. for 2 h., then cooled to room temperature, and carefully poured into saturated aqueous sodium bicarbonate. After the exotherm ceased, the mixture was extracted with ethyl acetate (2×). The combined organic layers were dried over sodium sulfate, filtered, and concentrated. The residue was purified by reverse phase HPLC (45:55 to 85:15 acetonitrile:water with a 0.1% trifluoroacetic acid modifier) to afford 5-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,3,6,7-tetrahydro-2H-azepin-2-one and 5-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,3,4,7-tetrahydro-2H-azepin-2-one (70:30 mixture, 119 mg, 0.26 mmol, 41% yield) as a yellow solid. MS ESI: [M+H]+ m/z 446.1.

Workup

  1. temperaturecooled to room temperature
  2. extractionthe mixture was extracted with ethyl acetate (2×)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by reverse phase HPLC (45:55 to 85:15 acetonitrile

Sources & evidence

ORD record
ord-ce8e5279ebf7488c899c21e6bb176729
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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