1-(5-(4-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-ylamino)-5-fluoropyrimidin-2-ylamino)-4-fluoro-2-(3-hydroxyprop-1-ynyl)phenyl)-4-methyl-1H-tetrazol-5(4H)-one → 1-(5-(4-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-ylamino)-5-fluoropyrimidin-2-ylamino)-4-fluoro-2-(3-hydroxypropyl)phenyl)-4-methyl-1H-tetrazol-5(4H)-one

HRID 633399Notes

Reaction equation

HRID 633399 reaction equation
[CH3:1][C:2]1([CH3:38])[CH2:10][C@H:9]([NH:11][C:12]2[C:17]([F:18])=[CH:16][N:15]=[C:14]([NH:19][C:20]3[C:21]([F:37])=[CH:22][C:23]([C:33]#[C:34][CH2:35][OH:36])=[C:24]([N:26]4[C:30](=[O:31])[N:29]([CH3:32])[N:28]=[N:27]4)[CH:25]=3)[N:13]=2)[CH2:8][C@H:7]2[N:3]1[CH2:4][CH2:5][CH2:6]2>CO.[Pd]>[CH3:1][C:2]1([CH3:38])[CH2:10][C@H:9]([NH:11][C:12]2[C:17]([F:18])=[CH:16][N:15]=[C:14]([NH:19][C:20]3[C:21]([F:37])=[CH:22][C:23]([CH2:33][CH2:34][CH2:35][OH:36])=[C:24]([N:26]4[C:30](=[O:31])[N:29]([CH3:32])[N:28]=[N:27]4)[CH:25]=3)[N:13]=2)[CH2:8][C@H:7]2[N:3]1[CH2:4][CH2:5][CH2:6]2

Participants

4

Reactant 1

HCID 867044971-(5-(4-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-ylamino)-5-fluoropyrimidin-2-ylamino)-4-fluoro-2-(3-hydroxyprop-1-ynyl)phenyl)-4-methyl-1H-tetrazol-5(4H)-one

Product 1

HCID 867044981-(5-(4-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-ylamino)-5-fluoropyrimidin-2-ylamino)-4-fluoro-2-(3-hydroxypropyl)phenyl)-4-methyl-1H-tetrazol-5(4H)-oneYield 63%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

1-(5-(4-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-ylamino)-5-fluoropyrimidin-2-ylamino)-4-fluoro-2-(3-hydroxyprop-1-ynyl)phenyl)-4-methyl-1H-tetrazol-5(4H)-one (77.9 mg, 0.15 mmol) was dissolved in 10 mL methanol. After purging with nitrogen, the flask was charged with 32.7 mg (0.015 mmol) 10% palladium on carbon (50 wt % water for safety). The reaction was then evacuated and back-filled with nitrogen three times before one final evacuation and introduction of a hydrogen balloon. This was stirred overnight at room temperature under one atmosphere of hydrogen. After filtration of the catalyst, the methanol was evaporated to give 72.6 mg (93% crude recovery). 63.0 mg was subjected to column chromatography. After drying, 39.6 mg was obtained of the title compound (63% yield).

Workup

  1. customAfter purging with nitrogen
  2. customThe reaction was then evacuated
  3. additionback-filled with nitrogen three times before one final evacuation and introduction of a hydrogen balloon
  4. filtrationAfter filtration of the catalyst
  5. customthe methanol was evaporated
  6. customto give 72.6 mg (93% crude recovery)
  7. customAfter drying

Sources & evidence

ORD record
ord-d68ba5d5302b4be59fdac1bc62f36049
Source dataset
uspto-grants-2016_04
Patent number
US09321763B2

Reaction notes

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