Picolinic acid → HCID 46189104, compound

HRID 537800Notes

Reaction equation

HRID 537800 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13]2[CH:18]=[CH:17][N:16]3[N:19]=[CH:20][C:21]([NH2:22])=[C:15]3[N:14]=2)[CH:5]=[CH:6][CH:7]=1.[N:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[C:29](O)=[O:30].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CCOC(C)=O.CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([C@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13]2[CH:18]=[CH:17][N:16]3[N:19]=[CH:20][C:21]([NH:22][C:29](=[O:30])[C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][N:23]=4)=[C:15]3[N:14]=2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 1018Picolinic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67329531(R)-5-(2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine

Product 1

HCID 46189104HCID 46189104, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of (R)-5-(2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine (Example 6, Step A; 30 mg, 0.1 mmol), picolinic acid (15 mg, 0.12 mmol), and HATU (46 mg, 0.12 mmol) was added 0.7 mL DMF to make a solution. After cooling in an ice bath for 10 minutes, DIEA (0.053 mL, 0.3 mmol) was added to the reaction drop-wise. The reaction was allowed to warm up to ambient temperature and stirred for 10 minutes. The reaction mixture was diluted with EtOAc (15 mL), washed with water and brine (5 mL each), concentrated, and purified by reverse-phase column chromatography, eluting with 5 to 70% acetonitrile/water to yield the final product as a yellowish solid (35 mg, 86% yield). MS (apci) m/z=403.2 (M+H).

Workup

  1. temperatureAfter cooling in an ice bath for 10 minutes
  2. washwashed with water and brine (5 mL each)
  3. concentrationconcentrated
  4. custompurified by reverse-phase column chromatography
  5. washeluting with 5 to 70% acetonitrile/water

Sources & evidence

ORD record
ord-1d10c90147324a48a1562e7775d3c696
Source dataset
uspto-grants-2014_10
Patent number
US08865698B2

Reaction notes

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