Sodium hydride → Methyl {4,6-diamino-2-[6-fluoro-3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]pyrimidin-5-yl}(2,2,2-trifluoroethyl)carbamate

HRID 626620Notes

Reaction equation

HRID 626620 reaction equation
[NH2:1][C:2]1[C:7]([NH:8][C:9](=[O:12])[O:10][CH3:11])=[C:6]([NH2:13])[N:5]=[C:4]([N:14]2[C:22]3[C:17](=[N:18][CH:19]=[C:20]([F:23])[CH:21]=3)[C:16]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[F:31])=[N:15]2)[N:3]=1.[H-].[Na+].ClC(Cl)(Cl)S(O[CH2:40][C:41]([F:44])([F:43])[F:42])(=O)=O>C1COCC1.C(OCC)(=O)C>[NH2:1][C:2]1[C:7]([N:8]([CH2:40][C:41]([F:44])([F:43])[F:42])[C:9](=[O:12])[O:10][CH3:11])=[C:6]([NH2:13])[N:5]=[C:4]([N:14]2[C:22]3[C:17](=[N:18][CH:19]=[C:20]([F:23])[CH:21]=3)[C:16]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[F:31])=[N:15]2)[N:3]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 900272,2,2-Trifluoroethyl trichloromethanesulphonateHCID 56963347Methyl {4,6-diamino-2-[6-fluoro-3-(2-fluorobenzyl)-1H-pyrazolo [4,3-b]pyridin-1-yl]pyrimidin-5-yl}carbamate

Product 1

HCID 57335321Methyl {4,6-diamino-2-[6-fluoro-3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]pyrimidin-5-yl}(2,2,2-trifluoroethyl)carbamate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Under argon, 142 mg (0.33 mmol) of the compound from example 1 were initially charged in THF (9.5 ml), the mixture was cooled to 0° C. and 13 mg (0.33 mmol) of sodium hydride (60% suspension in mineral oil) were then added. The mixture was stirred at 0° C. for 30 min, and 96 μl (0.67 mmol) of 2,2,2,-trifluoroethyl trichloromethanesulfonate were then added dropwise. The reaction mixture was stirred at RT overnight. The mixture was then diluted with ethyl acetate and the organic phase was washed twice with saturated aqueous sodium bicarbonate solution. The organic phase was dried over magnesium sulfate, filtered and concentrated. The residue was chromatographed on silica gel (mobile phase dichloromethane:methanol 60:1) and the product fractions were concentrated. The crude product obtained in this manner was re-purified by means of preparative RP-HPLC (acetonitrile:water (+0.1% formic acid)−gradient), then suspended in acetonitrile/water and finally dried by lyophilization. This gave 68 mg (40% of theory) of the title compound as a solid.

Workup

  1. stirringThe reaction mixture was stirred at RT overnight
  2. washthe organic phase was washed twice with saturated aqueous sodium bicarbonate solution
  3. dry with materialThe organic phase was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was chromatographed on silica gel (mobile phase dichloromethane:methanol 60:1)
  7. concentrationthe product fractions were concentrated

Sources & evidence

ORD record
ord-575fd3ede042418eb05f03cf24efc97e
Source dataset
uspto-grants-2016_04
Patent number
US09309239B2

Reaction notes

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