1,1'-Carbonyldiimidazole → (S)-N-(5-((R)-2-(5-fluoropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide

HRID 64029Notes

Reaction equation

HRID 64029 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]=[N:6][CH:7]=1.C1N=CN([C:28]([N:30]2[CH:34]=N[CH:32]=[CH:31]2)=[O:29])C=1.N1CC[C@H:37]([OH:40])C1>C(Cl)Cl>[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:28]([N:30]4[CH2:31][CH2:32][C@H:37]([OH:40])[CH2:34]4)=[O:29])=[C:15]3[N:14]=2)[CH:5]=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 2733874(3S)-pyrrolidin-3-olHCID 67328765(R)-5-(2-(5-fluoropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine

Product 1

HCID 58386263(S)-N-(5-((R)-2-(5-fluoropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamideYield 78.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a DCM (1 mL) solution of (R)-5-(2-(5-fluoropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine (25 mg, 0.084 mmol) was added CDI (27 mg, 0.17 mmol) at ambient temperature in one portion. After stirring for two hours, (S)-pyrrolidin-3-ol (15 mg, 0.17 mmol) was added in one portion. The reaction was stirred overnight before it was concentrated and directly purified by reverse-phase column chromatography, eluting with 0 to 40% acetonitrile/water to yield the final product as a solid (27 mg, 78% yield). MS (apci) m/z=412.2 (M+H).

Workup

  1. stirringThe reaction was stirred overnight before it
  2. concentrationwas concentrated
  3. customdirectly purified by reverse-phase column chromatography
  4. washeluting with 0 to 40% acetonitrile/water

Sources & evidence

ORD record
ord-bbc0085fd8ec45a39d4ea52682ffd833
Source dataset
uspto-grants-2016_09
Patent number
US09447104B2

Reaction notes

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