Hydrochloric Acid → HCID 11350611, compound

HRID 2105210Notes

Reaction equation

HRID 2105210 reaction equation
[BH4-].[Li+].C[O:4][C:5]([C:7]1[N:12]=[C:11]([N:13]2[CH2:17][CH2:16][CH2:15][CH:14]2[C:18]2[O:22][N:21]=[C:20]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=3)[CH:19]=2)[N:10]=[C:9]([NH:29][C:30]2[CH:34]=[C:33]([CH3:35])[NH:32][N:31]=2)[CH:8]=1)=O.CO.Cl>C1COCC1.O1CCOCC1>[OH:4][CH2:5][C:7]1[N:12]=[C:11]([N:13]2[CH2:17][CH2:16][CH2:15][CH:14]2[C:18]2[O:22][N:21]=[C:20]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=3)[CH:19]=2)[N:10]=[C:9]([NH:29][C:30]2[CH:34]=[C:33]([CH3:35])[NH:32][N:31]=2)[CH:8]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 4148881Lithium borohydrideHCID 113053826-Methoxycarbonyl-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-1-yl}-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidine

Product 1

HCID 11350611HCID 11350611, compoundYield 91%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

A 2M solution of lithium borohydride in THF (22.4 ml, 44.8 mmol) was added to a mixture of 6-methoxycarbonyl-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-1-yl}-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidine (Example 56) (4.0 mg, 8.96 mmol) in anhydrous THF (200 ml). The reaction mixture was stirred at ambient temperature for 3 hours and then heated at reflux for 1 hour. The mixture allowed to cool and methanol was added until effervescence ceased, a 4M solution hydrogen chloride in dioxane (30 ml) was then added and the mixture heated at reflux for 1 hour. The volatiles were removed by evaporation, the residue was dissolved in water and the resulting solution adjusted to pH 9 by careful addition of 10M aqueous sodium hydroxide solution. The aqueous mixture was extracted with DCM and purification by chromatography on silica gel, eluting with DCM/methanol (100:0 increasing in polarity to 90:10) to give the title compound (3.4 g, 91%).

Workup

  1. temperatureheated
  2. temperatureat reflux for 1 hour
  3. temperatureto cool
  4. temperaturethe mixture heated
  5. temperatureat reflux for 1 hour
  6. customThe volatiles were removed by evaporation
  7. dissolutionthe residue was dissolved in water
  8. additionthe resulting solution adjusted to pH 9 by careful addition of 10M aqueous sodium hydroxide solution
  9. extractionThe aqueous mixture was extracted with DCM and purification by chromatography on silica gel
  10. washeluting with DCM/methanol (100:0 increasing in polarity to 90:10)

Sources & evidence

ORD record
ord-a25f85f5cd3747c9b8a8752d8e2fee10
Source dataset
uspto-grants-2009_08
Patent number
US07579349B2

Reaction notes

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