HCID 68085472, compound → HCID 66604497, compound

HRID 2410871Notes

Reaction equation

HRID 2410871 reaction equation
[C:1]([C:4]1[C:16]2[NH:15][C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:17]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[O:18])[CH:13]=3)[C:8]=2[CH:7]=[C:6]([C:25]2[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH:26]=2)[CH:5]=1)(=[O:3])[NH2:2]>CCO.[Pd]>[C:1]([C:4]1[C:16]2[NH:15][C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:17]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[O:18])[CH:13]=3)[C:8]=2[CH:7]=[C:6]([CH:25]2[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]2)[CH:5]=1)(=[O:3])[NH2:2]

Participants

4

Reactant 1

HCID 68085472HCID 68085472, compound

Product 1

HCID 66604497HCID 66604497, compoundYield 64.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

tert-Butyl 4-(1-carbamoyl-7-(morpholine-4-carbonyl)-9H-carbazol-3-yl)-5,6-dihydropyridine-1(2H)−carboxylate (Example 390, 159 mg, 0.290 mmol) was dissolved in EtOH (50 ml) in a 500-ml PARR flask. The flask was flushed with nitrogen, than palladium (10% on carbon, 96 mg, 0.090 mmol) was added, the flask flushed with nitrogen again, then transferred onto PARR shaker and hydrogenated for 24 hours under 60 psi of hydrogen. The reaction mixture was filtered through a 0.45 uM nylon filter and concentrated in vacuum. 94.3 mg crude tert-butyl 4-(1-carbamoyl-7-(morpholine-4-carbonyl)-9H-carbazol-3-yl)piperidine-1-carboxylate (colorless film) was isolated. 44.3 mg of the crude were purified by preparative HPLC to give 21.5 mg tert-butyl 4-(1-carbamoyl-7-(morpholine-4-carbonyl)-9H-carbazol-3-yl)piperidine-1-carboxylate. MS m/e+=507, m/e−505 consistent with [M−H]− and [M+H]+. 1H NMR (CD3OD) δ ppm 8.21 (s, 1H), 8.20 (d, 1H, J=8.0), 7.86 (d, 1H, J=1.5), 7.67 (s, 1H), 7.26 (dd, 1H, J=8.0, 1.5), 4.29 (bd, 2H, J=13.3), 3.90-3.50 (b, 8H), 2.95 (m, 3H), 1.96 (br. d. 2H, J˜12), 1.79 (dq, 2H, J=4.1, 12.6), 1.51 (s, 9H).

Workup

  1. additionwas added
  2. customthe flask flushed with nitrogen again
  3. filtrationThe reaction mixture was filtered through a 0.45 uM nylon
  4. filtrationfilter
  5. concentrationconcentrated in vacuum

Sources & evidence

ORD record
ord-4e831c8e06cc431a953546f58edc0f01
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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