1,1'-Carbonyldiimidazole → (R)-N-(5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-4-isopropylpiperazine-1-carboxamide

HRID 64005Notes

Reaction equation

HRID 64005 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]([NH2:23])=[C:16]2[N:15]=1.C1N=CN([C:29](N2C=NC=C2)=[O:30])C=1.[CH:36]([N:39]1[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1)([CH3:38])[CH3:37]>C(Cl)Cl>[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]([NH:23][C:29]([N:42]3[CH2:43][CH2:44][N:39]([CH:36]([CH3:38])[CH3:37])[CH2:40][CH2:41]3)=[O:30])=[C:16]2[N:15]=1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 780131-IsopropylpiperazineHCID 58386314(R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine

Product 1

HCID 46188931(R)-N-(5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-4-isopropylpiperazine-1-carboxamideYield 90%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a DCM (0.8 mL) solution of (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine (Preparation B; 30 mg, 0.095 mmol) was added CDI (31 mg, 0.19 mmol) at ambient temperature in one portion. After stirring two hours, 1-isopropylpiperazine (24 mg, 0.19 mmol) was added in one portion. The reaction was stirred for 5 minutes before it was concentrated and directly purified by reverse-phase column chromatography, eluting with 5 to 45% acetonitrile/water to yield the final product as a yellowish foamy powder (40 mg, 90% yield). MS (apci) m/z=470.1 (M+H).

Workup

  1. stirringThe reaction was stirred for 5 minutes before it
  2. concentrationwas concentrated
  3. customdirectly purified by reverse-phase column chromatography
  4. washeluting with 5 to 45% acetonitrile/water

Sources & evidence

ORD record
ord-edf45de5ccc84738beb8474678ec68bc
Source dataset
uspto-grants-2016_09
Patent number
US09447104B2

Reaction notes

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