Hydrochloric Acid → HCID 178502990, compound

HRID 1821592Notes

Reaction equation

HRID 1821592 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:16]2[C:11](=[N:12][C:13]([O:22][C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[F:30])=[N:14][C:15]=2[NH:17][CH2:18][C@@H:19]([OH:21])[CH3:20])[NH:10][N:9]=1.[P:31]([O:36]C)([O:34][CH3:35])[O:32][CH3:33].C(Br)(Br)(Br)Br.Cl>N1C=CC=CC=1>[CH3:33][O:32][P:31](=[O:36])([O:34][CH3:35])[O:21][CH:19]([CH3:20])[CH2:18][NH:17][C:15]1[N:14]=[C:13]([O:22][C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=2[F:30])[N:12]=[C:11]2[NH:10][N:9]=[C:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])[C:16]=12

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8472Trimethyl phosphiteHCID 11205Carbon tetrabromideHCID 178462355HCID 178462355, compound

Product 1

HCID 178502990HCID 178502990, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

(S)-1-[3-(2-chlorophenyl)-6-(2,4-difluorophenoxy)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]propan-2-ol (2.5 g, 5.79 mmol) was dissolved in 20 mL pyridine at room temperature, and the mixture was cooled to 0° C. with stirring. P(OCH3)3 (1.93 mL, excess) and CBr4 (0.96 g) were added slowly, and the reaction mixture was allowed to warm up to room temperature over 20 minutes with stirring. The reaction mixture was poured into cold 1N HCl, and the resulting solution was extracted with EtOAc. The combined organic layers were washed with 1N HCl, followed by saturated aqueous NaHCO3, then with saturated brine. The organic phase was dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, 30%-60% EtOAc in methylene chloride) to give 3.132 g of phosphoric acid 2-[3-(2-chloro-phenyl)-6-(2,4-difluoro-phenoxy)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-1-methyl-ethyl ester dimethyl ester, MS (M+H)=540.

Workup

  1. temperatureto warm up to room temperature over 20 minutes
  2. stirringwith stirring
  3. extractionthe resulting solution was extracted with EtOAc
  4. washThe combined organic layers were washed with 1N HCl
  5. dry with materialThe organic phase was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash chromatography (silica gel, 30%-60% EtOAc in methylene chloride)

Sources & evidence

ORD record
ord-5cb2cc46416d4ccd8924dcaa49cd2303
Source dataset
uspto-grants-2009_10
Patent number
US07608603B2

Reaction notes

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