Water → HCID 11154288, compound

HRID 2105214Notes

Reaction equation

HRID 2105214 reaction equation
[N-:1]=[N+]=[N-].[Na+].CC1C=CC(S(O[CH2:16][C:17]2[N:22]=[C:21]([N:23]3[CH2:27][CH2:26][CH2:25][CH:24]3[C:28]3[O:32][N:31]=[C:30]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=4)[CH:29]=3)[N:20]=[C:19]([NH:39][C:40]3[CH:44]=[C:43]([CH3:45])[N:42](S(C4C=CC(C)=CC=4)(=O)=O)[N:41]=3)[CH:18]=2)(=O)=O)=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>CN(C=O)C>[NH2:1][CH2:16][C:17]1[N:22]=[C:21]([N:23]2[CH2:27][CH2:26][CH2:25][CH:24]2[C:28]2[O:32][N:31]=[C:30]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=3)[CH:29]=2)[N:20]=[C:19]([NH:39][C:40]2[CH:44]=[C:43]([CH3:45])[NH:42][N:41]=2)[CH:18]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11776TriphenylphosphineHCID 33557Sodium AzideHCID 86610855HCID 86610855, compound

Product 1

HCID 11154288HCID 11154288, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

Sodium azide (44 mg, 0.68 mmol) was added to a solution of 6-[(4-methylphenylsulphonyloxy)methyl]-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-1-yl}-4-(5-methyl-1-N-[4-methylphenylsulphonyl]-1H-pyrazol-3-ylamino)pyrimidine (Method 52) (159 mg, 0.22 mmol) in anhydrous DMF (2.0 ml) and the mixture heated at 110° C. for 1.5 hours. Triphenylphosphine (282.0 mg, 1.08 mmol) and water (0.10 ml) were then added and the reaction mixture heated at 100° C. for 1 hour. The mixture allowed to cool and was then passed through a 50 g isolute SCX-2 ion exchange column. The column was eluted with methanol to elute any neutrals, followed by 7M methanolic ammonia to elute the product. The volatiles were removed by evaporation and the residue dissolved in methanol (5 ml) and 10M aqueous sodium hydroxide solution (0.5 ml) and stirred for 1 hour. The volatiles were removed by evaporation and the residue dissolved in water, and extracted with DCM. The extracts were combined, the solvent removed by evaporation and the residue purified by chromatography on silica gel, eluting with DCM/methanol/aqueous ammonia (100:0:0 increasing in polarity to 80:20:1) to give the title compound (48.5 mg, 53%) as a solid.

Workup

  1. temperaturethe reaction mixture heated at 100° C. for 1 hour
  2. temperatureto cool
  3. washThe column was eluted with methanol
  4. washto elute any neutrals
  5. washto elute the product
  6. customThe volatiles were removed by evaporation
  7. dissolutionthe residue dissolved in methanol (5 ml)
  8. customThe volatiles were removed by evaporation
  9. dissolutionthe residue dissolved in water
  10. extractionextracted with DCM
  11. customthe solvent removed by evaporation
  12. customthe residue purified by chromatography on silica gel
  13. washeluting with DCM/methanol/aqueous ammonia (100:0:0 increasing in polarity to 80:20:1)

Sources & evidence

ORD record
ord-8611a9aeca1c4bd9b3c3324ab5f3e206
Source dataset
uspto-grants-2009_08
Patent number
US07579349B2

Reaction notes

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