Dimethylformamide → HCID 76687048, compound

HRID 2178181Notes

Reaction equation

HRID 2178181 reaction equation
CN(C=O)C.FC(F)(F)C(O)=O.[F:13][C:14]1[C:19]([CH3:20])=[CH:18][C:17]([NH:21][C:22]2[N:27]=[C:26]([NH:28][C:29]3[CH:30]=[CH:31][C:32]4[O:36][C:35](=[O:37])[NH:34][C:33]=4[CH:38]=3)[C:25]([CH3:39])=[CH:24][N:23]=2)=[CH:16][C:15]=1[O:40][CH3:41].C([O-])([O-])=O.[Cs+].[Cs+].[P:48]([O:60][CH2:61]Cl)([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49]>O>[P:48]([O:60][CH2:61][N:34]1[C:33]2[CH:38]=[C:29]([NH:28][C:26]3[C:25]([CH3:39])=[CH:24][N:23]=[C:22]([NH:21][C:17]4[CH:18]=[C:19]([CH3:20])[C:14]([F:13])=[C:15]([O:40][CH3:41])[CH:16]=4)[N:27]=3)[CH:30]=[CH:31][C:32]=2[O:36][C:35]1=[O:37])([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])([O:55][C:56]([CH3:57])([CH3:58])[CH3:59])=[O:49]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 11701630Di-tert-butyl (chloromethyl) phosphate2×HCID 66713692HCID 66713692, compound

Product 1

HCID 76687048HCID 76687048, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

With reference to Scheme (XI), A DMF (300 mL) suspension of 5-(2-(4-fluoro-3-methoxy-5-methylphenylamino)-5-methylpyrimidin-4-ylamino)benzo[d]oxazol-2(3H)-one trifluoroacetate (prepared as described in Example 3) (40.38 g, 79 mmol) and Cs2CO3 (78.3 g, 238 mmol) was stirred at rt under Nitrogen atmosphere, after 2.5 h, di-tert-butyl chloromethyl phosphate (26.6 g, 103 mmol) was added and stirring was continued at room temperature. After 49 h, by LC-MS, the reaction was >90% complete (note: due to relatively poor quality of alkylating agent of this batch, additional ˜7 g of di-tert-butyl chloromethyl phosphate was added). With stirring, the reaction mixture was poured into 1.2 L of H2O, ppt formed and was a bit lumpy, additional 500 mL of H2O was added to ensure the formation of non-sticky solid. Precipitate was collected by filtration, washed with water, and was further dried under high vac. Compound di-tert-butyl (5-(2-(4-fluoro-3-methoxy-5-methylphenylamino)-5-methylpyrimidin-4-ylamino)-2-oxobenzo[d]oxazol-3(2H)-yl)methyl phosphate was obtained as a light brown solid and was used directly in the next reaction.

Workup

  1. stirringstirring
  2. customwas continued at room temperature
  3. waitAfter 49 h
  4. additionwas added)
  5. stirringWith stirring
  6. customformed
  7. additionwas added
  8. filtrationPrecipitate was collected by filtration
  9. washwashed with water
  10. customwas further dried under high vac

Sources & evidence

ORD record
ord-b58f27cc10754ee38c3484f0bbc8469a
Source dataset
uspto-grants-2015_06
Patent number
US09067925B2

Reaction notes

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