Diisopropylethylamine → 5-[4,4-Difluoro-2-(isoxazol-3-ylcarbonyl)octahydro-4aH-cyclopropa[3,4]-cyclopenta[1,2-c]pyrrol-4a-yl]-1-(2,2-dimethylpropyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

HRID 629903Notes

Reaction equation

HRID 629903 reaction equation
[F:1][C:2]1([F:27])[C:4]2([C:11]3[N:16]=[C:15]4[N:17]([CH3:26])[C:18](=[O:25])[N:19]([CH2:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C:14]4=[CH:13][CH:12]=3)[CH2:5][CH:6]3[CH:10]([CH:3]12)[CH2:9][NH:8][CH2:7]3.[O:28]1[CH:32]=[CH:31][C:30]([C:33](O)=[O:34])=[N:29]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(#N)C>[F:27][C:2]1([F:1])[C:4]2([C:11]3[N:16]=[C:15]4[N:17]([CH3:26])[C:18](=[O:25])[N:19]([CH2:20][C:21]([CH3:24])([CH3:22])[CH3:23])[C:14]4=[CH:13][CH:12]=3)[CH2:5][CH:6]3[CH:10]([CH:3]12)[CH2:9][N:8]([C:33]([C:30]1[CH:31]=[CH:32][O:28][N:29]=1)=[O:34])[CH2:7]3

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 112864533-Isoxazolecarboxylic acidHCID 711366875-(4,4-Difluorooctahydro-4aH-cyclopropa[3,4]cyclopenta[1,2-c]pyrrol-4a-yl)-1-(2,2-dimethylpropyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

Product 1

HCID 711366725-[4,4-Difluoro-2-(isoxazol-3-ylcarbonyl)octahydro-4aH-cyclopropa[3,4]-cyclopenta[1,2-c]pyrrol-4a-yl]-1-(2,2-dimethylpropyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

5-(4,4-Difluorooctahydro-4aH-cyclopropa[3,4]cyclopenta[1,2-c]pyrrol-4a-yl)-1-(2,2-dimethylpropyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (30-3, 50 mg, 0.14 mmol, 1.0 equiv), isoxazole-3-carboxylic acid (2-6, 22.5 mg, 0.20 mmol, 1.5 equiv), DIPEA (0.070 mL, 0.40 mmol, 3.0 equiv) and HATU (76 mg, 0.20 mmol, 1.5 equiv) were added to anhydrous acetonitrile (1 mL). After stirring for 10 min at room temperature, LCMS showed consumption of starting material. Purification by reverse-phase HPLC (20-100% CH3CN:0.1% TFA in H2O) provided 30-4 as a white solid. MS m/z (M+H): calculated=472.2155; observed=472.2153.

Workup

  1. customconsumption of starting material
  2. customPurification by reverse-phase HPLC (20-100% CH3CN:0.1% TFA in H2O)

Sources & evidence

ORD record
ord-441a8add706146538b1f6bcac88d7c25
Source dataset
uspto-grants-2016_04
Patent number
US09315518B2

Reaction notes

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