3-Amino-1-propanol → (R)-5-(2-(5-fluoro-2-methoxypyridin-3-yl)pyrrolidin-1-yl)-N-(3-hydroxypropyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 1426908Notes

Reaction equation

HRID 1426908 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]2[CH:20]=[CH:19][N:18]3[N:21]=[CH:22][C:23]([C:24](O)=[O:25])=[C:17]3[N:16]=2)[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:51][CH2:52][CH2:53][CH2:54][OH:55].CCN(C(C)C)C(C)C>C(#N)C.O.CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([C@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]2[CH:20]=[CH:19][N:18]3[N:21]=[CH:22][C:23]([C:24]([NH:51][CH2:52][CH2:53][CH2:54][OH:55])=[O:25])=[C:17]3[N:16]=2)[C:5]([O:8][CH3:9])=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 90863-Amino-1-propanolHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66847769HCID 66847769, compound

Product 1

HCID 67471053(R)-5-(2-(5-fluoro-2-methoxypyridin-3-yl)pyrrolidin-1-yl)-N-(3-hydroxypropyl)pyrazolo[1,5-a]pyrimidine-3-carboxamideYield 69%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
0 °C

Procedure

To a DMF (2 mL) suspension of (R)-5-(2-(5-fluoro-2-methoxy pyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (Preparation B, 250 mg, 0.700 mmol) and HATU (319 mg, 0.840 mmol) cooled to 0° C. was added 3-aminopropan-1-ol (0.0642 mL, 0.840 mmol) drop-wise, resulting in a clear yellowish solution. After dropwise addition of DIEA (0.366 mL, 2.10 mmol), ice bath was removed and reaction was stirred at ambient temperature for 1 hour. The reaction was directly purified on reverse phase column chromatography (Biotage SP4 system, C-18 25+M column, 0 to 54% Acetonitrile/water), to provide the product as white solid (200 mg, 69% yield). MS (apci) m/z=415.1 (M+H).

Workup

  1. customresulting in a clear yellowish solution
  2. customwas removed
  3. customreaction
  4. customThe reaction was directly purified on reverse phase column chromatography (Biotage SP4 system

Sources & evidence

ORD record
ord-ea4722f074224389b6c6c8808767f49a
Source dataset
uspto-grants-2015_01
Patent number
US08933084B2

Reaction notes

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