Sodium Hydroxide → 1357103-62-8

HRID 1797927Notes

Reaction equation

HRID 1797927 reaction equation
[P:1]([OH:35])([OH:34])([O:3][CH2:4][N:5]1[C:9]2[CH:10]=[C:11]([NH:14][C:15]3[C:20]([CH3:21])=[CH:19][N:18]=[C:17]([NH:22][C:23]4[CH:28]=[C:27]([CH3:29])[C:26]([F:30])=[C:25]([O:31][CH3:32])[CH:24]=4)[N:16]=3)[CH:12]=[CH:13][C:8]=2[O:7][C:6]1=[O:33])=[O:2].[OH-].[Na+:37]>O>[P:1]([O-:35])([O-:34])([O:3][CH2:4][N:5]1[C:9]2[CH:10]=[C:11]([NH:14][C:15]3[C:20]([CH3:21])=[CH:19][N:18]=[C:17]([NH:22][C:23]4[CH:28]=[C:27]([CH3:29])[C:26]([F:30])=[C:25]([O:31][CH3:32])[CH:24]=4)[N:16]=3)[CH:12]=[CH:13][C:8]=2[O:7][C:6]1=[O:33])=[O:2].[Na+:37].[Na+:37]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 580713852(3H)-Benzoxazolone, 5-[[2-[(4-fluoro-3-methoxy-5-methylphenyl)amino]-5-methyl-4-pyrimidinyl]amino]-3-[(phosphonooxy)methyl]-

Product 1

HCID 665748831357103-62-8Yield 89%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

With stirring, to a H2O (500 mL) suspension of crude (5-(2-(4-fluoro-3-methoxy-5-methylphenylamino)-5-methylpyrimidin-4-ylamino)-2-oxobenzo[d]oxazol-3(2H)-yl)methyl dihydrogen phosphate, 1N NaOH (aq., 163 mL, 163 mmol) was added dropwise over 15 min, with ice-bath cooling. Remove ice-bath, add additional H2O until final volume reaching ˜1 L. Solid was removed by filtration through a filter paper, washing with H2O Solid (˜3 g) appeared as a 1:1 mixture of prodrug and parent compound (I-105) which was formed during previous hydrolysis reaction.). Filtrate was collected, and most H2O was removed by lyophilization (˜20 mL of H2O left as solid ice). With stirring, i-PrOH (800 mL) was added to the solid, stirring was continued for 1 h until solid was evenly dispersed in the solution. Solid was collected by filtration, washed with i-PrOH (˜100 mL×3), and was further dried under high vac. Compound disodium (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 beige color solid: 38.87 g (89% yield over 3 steps, starting from the TFA salt described above); 1H NMR (300 MHz, D2O) δ 7.63 (s, 1H), 7.39-7.33 (m, 2H), 7.13-7.09 (m, 1H), 6.77-6.71 (m, 2H), 5.41 (d, J=6.1 Hz, 2H), 3.62 (s, 3H), 2.01 (br s, 3H), 1.99 (br s, 3H); LRMS (M−) m/z 504.12.

Workup

  1. additionwas added dropwise over 15 min, with ice-bath
  2. temperaturecooling
  3. customSolid was removed by filtration through a filter paper
  4. washwashing with H2O Solid (˜3 g)
  5. additionappeared as a 1:1 mixture of prodrug
  6. customparent compound (I-105) which was formed during previous hydrolysis reaction
  7. customFiltrate was collected
  8. custommost H2O was removed by lyophilization (˜20 mL of H2O left as solid ice)
  9. additioni-PrOH (800 mL) was added to the solid
  10. stirringstirring
  11. additionwas evenly dispersed in the solution
  12. filtrationSolid was collected by filtration
  13. washwashed with i-PrOH (˜100 mL×3)
  14. customwas further dried under high vac

Sources & evidence

ORD record
ord-dd52920c982640c5a7c4d81bd7012230
Source dataset
uspto-grants-2013_01
Patent number
US08343954B2

Reaction notes

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