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

HRID 626619Notes

Reaction equation

HRID 626619 reaction equation
[NH2:1][C:2]1[C:7](NC(=O)OC)=[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.C[Si]([N-:36][Si](C)(C)C)(C)C.[Na+].I[CH2:43][CH3:44].[C:45]([O:48][CH2:49]C)(=[O:47])C>C1COCC1>[NH2:13][C:6]1[C:7]([CH2:44][CH2:43][NH:36][C:45](=[O:47])[O:48][CH3:49])=[C:2]([NH2:1])[N:3]=[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:5]=1

Participants

6

Reactant 4

HCID 6340IodoethaneHCID 8857Ethyl AcetateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 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 86698876Methyl {4,6-diamino-2-[6-fluoro-3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]pyrimidin-5-yl}ethylcarbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

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 0.33 ml (0.33 mmol) of sodium bis(trimethylsilyl)amide (1.0 M in THF) was then added dropwise. The mixture was stirred at 0° C. for 30 min, and 35 μl (0.43 mmol) of iodoethane were then added dropwise. The reaction mixture was stirred at RT overnight. The reaction mixture was diluted with ethyl acetate and 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. This gave 89 mg (59% of theory) of the title compound as a solid.

Workup

  1. stirringThe reaction mixture was stirred at RT overnight
  2. washwashed 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-ee831e6ded404dda843f810e2978b050
Source dataset
uspto-grants-2016_04
Patent number
US09309239B2

Reaction notes

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