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

HRID 510036Notes

Reaction equation

HRID 510036 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]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[C:20]([F:23])[CH:21]=3)[N: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.O>C1COCC1>[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]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[C:20]([F:23])[CH:21]=3)[N: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 4

HCID 962WaterHCID 24758Sodium hydrideHCID 900272,2,2-Trifluoroethyl trichloromethanesulphonateHCID 54674461Vericiguat

Product 1

HCID 54754870Methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}(2,2,2-trifluoroethyl)carbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

3.470 g (8.138 mmol) of the compound from example 31A were suspended in 35 ml of THF, 358 mg (8.952 mmol) of sodium hydride (60% suspension in mineral oil) were added at 0° C. and the mixture was stirred at 0° C. for 90 min, forming a solution. 2.519 g (8.952 mmol) of 2,2,2-trifluoroethyl trichloromethanesulfonate were added and the mixture was stirred at RT for 48 h. The mixture was then stirred with water and concentrated on a rotary evaporator. The residue was taken up in ethyl acetate, and the organic phase was washed twice with water and dried over sodium sulfate. This gave 5.005 g of the target compound (79% of theory, purity by HPLC 65%). 250 mg of residue were purified by means of preparative HPLC (eluent: methanol/water, gradient 30:70→90:10).

Workup

  1. customforming a solution
  2. stirringthe mixture was stirred at RT for 48 h
  3. concentrationconcentrated on a rotary evaporator
  4. washthe organic phase was washed twice with water
  5. dry with materialdried over sodium sulfate
  6. custom250 mg of residue were purified by means of preparative HPLC (eluent: methanol/water, gradient 30:70→90:10)

Sources & evidence

ORD record
ord-9da33d40a6d24476b1bbbf474e49de35
Source dataset
uspto-grants-2015_08
Patent number
US09096592B2

Reaction notes

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