1,1'-Carbonyldiimidazole → (1S,4S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-2-oxa-5-azabicyclo[2.2.1]heptane-5-carboxamide

HRID 64031Notes

Reaction equation

HRID 64031 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.Cl.[C@H:37]12[CH2:43][C@H:40]([NH:41][CH2:42]1)[CH2:39][O:38]2.CCN(C(C)C)C(C)C>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:41]3[CH2:42][C@@H:37]4[CH2:43][C@H:40]3[CH2:39][O:38]4)=[O:30])=[C:16]2[N:15]=1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 21303398(1S,4S)-2-oxa-5-azabicyclo(2.2.1)heptane hydrochlorideHCID 58386314(R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine

Product 1

HCID 58386329(1S,4S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-2-oxa-5-azabicyclo[2.2.1]heptane-5-carboxamideYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a DCM (1.0 mL) solution of (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine (Preparation B; 50 mg, 0.16 mmol) was added CDI (51 mg, 0.32 mmol) at ambient temperature in one portion. After stirring 90 minutes, (1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane hydrochloride (43 mg, 0.32 mmol) was added in one portion, followed by DIEA (0.083 mL, 0.48 mmol). The reaction was stirred for 5 minutes before it was concentrated and directly purified by reverse-phase column chromatography, eluting with 0 to 60% acetonitrile/water to yield the final product as a pale-yellowish powder (60 mg, 86% yield). MS (apci) m/z=441.2 (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 0 to 60% acetonitrile/water

Sources & evidence

ORD record
ord-2d693c11ab144d4f9f31f92f2cddd452
Source dataset
uspto-grants-2016_09
Patent number
US09447104B2

Reaction notes

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