HCID 86672032, compound → HCID 49833677, compound

HRID 473893Notes

Reaction equation

HRID 473893 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:13][C:12](=[O:14])[CH2:11][CH2:10][N:9]2[C:15]([N:17]2[CH2:23][C:22]3[CH:24]=[C:25]([C:28]4[CH:29]=[C:30]5[NH:36][C:35]([NH:37]C(=O)OCC6C=CC=CC=6)=[N:34][C:31]5=[N:32][CH:33]=4)[CH:26]=[CH:27][C:21]=3[O:20][CH2:19][CH2:18]2)=[O:16])[CH:5]=[CH:6][CH:7]=1>C(O)(=O)C.[Pd]>[NH2:37][C:35]1[NH:36][C:30]2[C:31]([N:34]=1)=[N:32][CH:33]=[C:28]([C:25]1[CH:26]=[CH:27][C:21]3[O:20][CH2:19][CH2:18][N:17]([C:15]([N:9]4[CH2:10][CH2:11][C:12](=[O:14])[CH2:13][CH:8]4[C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=4)=[O:16])[CH2:23][C:22]=3[CH:24]=1)[CH:29]=2

Participants

4

Reactant 1

HCID 86672032HCID 86672032, compound

Product 1

HCID 49833677HCID 49833677, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolvent

Procedure

A solution of phenylmethyl [6-(4-{[2-(3-fluorophenyl)-4-oxopiperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-yl]carbamate (0.15 g, 0.24 mmol) in acetic acid (5 mL) was hydrogenated at 1 atm over 10% palladium on carbon (0.15 g) for 18 h. The catalyst was removed by filtration and the filtrate was concentrated. The resulting brown residue was dissolved in methanol and purified by preparative reverse phase HPLC to afford 1-{[7-(2-amino-1H-imidazo[4,5-b]pyridin-6-yl)-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]carbonyl}-2-(3-fluorophenyl)piperidin-4-one (46 mg, 39% yield) as a pale yellow solid. 1H NMR (400 MHz, CDCl3): 11.44 (bs, 1H), 8.17 (s, 1H), 6.97-7.60 (m, 7H), 6.75 (s, 1H), 5.18 (t, 1H), 4.51-4.66 (m, 2H), 4.13-4.30 (m, 2H), 3.56-3.78 (m, 3H), 3.21-3.31 (m, 1H), 2.79-2.99 (m, 2H), 2.51-2.61 (m, 1H), 2.32 (d, 1H); MS (EI) for C27H25FN6O3: 501 (MH+)

Workup

  1. customThe catalyst was removed by filtration
  2. concentrationthe filtrate was concentrated
  3. dissolutionThe resulting brown residue was dissolved in methanol
  4. custompurified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-6039dbaa9be14e5ba1ddc2e17f66a526
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

Loading…