Diisopropylethylamine → 5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-N-((S)-2,3-dihydroxypropyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 1631314Notes

Reaction equation

HRID 1631314 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[C:14]1[CH:19]=[CH:18][N:17]2[N:20]=[CH:21][C:22]([C:23](O)=[O:24])=[C:16]2[N:15]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:50][CH2:51][C@H:52]([OH:55])[CH2:53][OH:54].C(N(C(C)C)CC)(C)C>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[C:14]1[CH:19]=[CH:18][N:17]2[N:20]=[CH:21][C:22]([C:23]([NH:50][CH2:51][C@H:52]([OH:55])[CH2:53][OH:54])=[O:24])=[C:16]2[N:15]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 4409023-Amino-1,2-propanediol, (S)-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66847716(R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid

Product 1

HCID 668873595-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-N-((S)-2,3-dihydroxypropyl)pyrazolo[1,5-a]pyrimidine-3-carboxamideYield 42.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (Preparation C, 400 mg, 1.16 mmol), HATU (486 mg, 1.28 mmol), and (S)-3-aminopropane-1,2-diol (318 mg, 3.49 mmol) in dry DMF (3.0 mL) was stirred for 1-2 minutes at ambient temperature. Diisopropylethylamine (DIEA) (0.62 mL, 3.49 mmol) was added and the reaction was flushed with N2, sealed and stirred at ambient temperature for 18 hours. The reaction mixture was added to H2O (15 mL), mixed and extracted with EtOAc. The combined EtOAc extracts were washed with H2O, saturated NaHCO3 and dried over MgSO4/activated carbon. The solution was eluted through a SiO2 column eluting first with EtOAc then 10% MeOH/EtOAc. The 10% MeOH/EtOAc pool was concentrated and the residual, colorless glass was dissolved in a minimal amount of CH2Cl2. Hexane was added and the resulting white suspension was sonicated and concentrated to give the title product as a white solid (205 mg, 42%). MS (apci) m/z=418.1 (M+H).

Workup

  1. customthe reaction was flushed with N2
  2. customsealed
  3. stirringstirred at ambient temperature for 18 hours
  4. additionThe reaction mixture was added to H2O (15 mL)
  5. additionmixed
  6. extractionextracted with EtOAc
  7. washThe combined EtOAc extracts were washed with H2O, saturated NaHCO3
  8. dry with materialdried over MgSO4/activated carbon
  9. washThe solution was eluted through a SiO2 column
  10. washeluting first with EtOAc
  11. concentrationThe 10% MeOH/EtOAc pool was concentrated
  12. dissolutionthe residual, colorless glass was dissolved in a minimal amount of CH2Cl2
  13. additionHexane was added
  14. customthe resulting white suspension was sonicated
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-5e48e8a6589e4dc5ac20e48d6bfaea73
Source dataset
uspto-grants-2014_07
Patent number
US08791123B2

Reaction notes

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