Water → HCID 86715498, compound

HRID 2284590Notes

Reaction equation

HRID 2284590 reaction equation
[P:1]([O-:37])([O-:36])([O:3][C:4](C(C)(C)C)(C(C)(C)C)[N:5]1[CH:13]=[C:12]2[C:7]([CH:8]=[CH:9][C:10]([C:14]3[C:15]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[C:22]([CH3:27])[CH:21]=4)=[N:16][CH:17]=[CH:18][CH:19]=3)=[CH:11]2)=[N:6]1)=[O:2].O>CC(O)=O.CC(C)=O>[P:1]([OH:37])([OH:36])([O:3][CH2:4][N:5]1[CH:13]=[C:12]2[C:7]([CH:8]=[CH:9][C:10]([C:14]3[C:15]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[C:22]([CH3:27])[CH:21]=4)=[N:16][CH:17]=[CH:18][CH:19]=3)=[CH:11]2)=[N:6]1)=[O:2]

Participants

5

Reactant 2

HCID 962WaterHCID 86715499HCID 86715499, compound

Product 1

HCID 86715498HCID 86715498, compoundYield 72.6%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 180AcetoneSolvent

Procedure

Di-tert-butyl[5-(2-(4-fluoro-3-methylphenyl)pyridin-3-yl)-2H-indazol-2-yl]methyl phosphate (N2, 100 mg, 0.21 mmol) was dissolved in AcOH:H2O (0.5 mL, 4:1) and the clear homogenous solution heated at 60° C. After 1 h, analysis of the reaction mixture LC/MS indicated the 97% consumption of di-tert-butyl[5-(2-(4-fluoro-3-methylphenyl)pyridin-3-yl)-2H-indazol-2-yl]methyl phosphate leading to the desired product of [5-(2-(4-fluoro-3-methylphenyl)pyridin-3-yl)-2H-indazol-2-yl]methyl dihydrogen phosphate (AUC 85%). At this stage heating was discontinued and the reaction mixture was polish filtered by suction. Concentration of the filtrate by rotary evaporator under vacuum (water bath temp 26-28° C.) resulted in a thick viscous liquid which was diluted with acetone (7 mL). The white heterogenous suspension was stirred for 30 min and filtered. The filter cake was washed with acetone (25 mL) and suction dried for a period of 1 h. The collected filter cake was further processed by drying under high vacuum over P2O5 for 24 h to provide [5-(2-(4-fluoro-3-methylphenyl)pyridin-3-yl)-2H-indazol-2-yl]methyl dihydrogen phosphate (63 mg, 71%). 1H NMR (DMSO-d6): δ 8.64 (dd, 1H, J=0.5 and 4.7 Hz), 8.51 (s, 1H), 7.86 (d, 1H, J=7.6 Hz), 7.70 (s, 1H), 7.50-7.41 (app m, 3H), 7.00-6.88 (m, 3H), 6.05 (d, 2H, 3JPH=10 Hz), 2.13 (s, 3H). 19F NMR (DMSO-d6): δ −118.60. 31P NMR (DMSO-d6): δ −2.63. LCMS: 97%, MS (m/e) 414 (MH+).

Workup

  1. customthe 97% consumption of di-tert-butyl[5-(2-(4-fluoro-3-methylphenyl)pyridin-3-yl)-2H-indazol-2-yl]methyl phosphate leading to the desired product of [5-(2-(4-fluoro-3-methylphenyl)pyridin-3-yl)-2H-indazol-2-yl]methyl dihydrogen phosphate (AUC 85%)
  2. temperatureAt this stage heating
  3. filtrationfiltered by suction
  4. customConcentration of the filtrate by rotary evaporator under vacuum (water bath temp 26-28° C.)
  5. customresulted in a thick viscous liquid which
  6. filtrationfiltered
  7. washThe filter cake was washed with acetone (25 mL) and suction
  8. customdried for a period of 1 h
  9. filtrationThe collected filter cake
  10. dry with materialby drying under high vacuum over P2O5 for 24 h

Sources & evidence

ORD record
ord-4477da38a67d4f3f8a93228988ef4534
Source dataset
uspto-grants-2015_09
Patent number
US09145433B2

Reaction notes

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