Hydrochloric Acid → 3-[2(R)-Hydroxypropyl]amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1-[[2'-[(t-butoxycarbonylamino)methyl][1,1'-biphenyl]-4-yl]methyl]-1H-benzazepin-3(R)-yl]butanamide

HRID 1755796Notes

Reaction equation

HRID 1755796 reaction equation
C([O:8][C@H:9]([CH3:53])[CH2:10][NH:11][C:12]([CH3:52])([CH3:51])[CH2:13][C:14]([NH:16][C@@H:17]1[CH2:23][CH2:22][C:21]2[CH:24]=[CH:25][CH:26]=[CH:27][C:20]=2[N:19]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[CH2:41][NH:42][C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])=[CH:31][CH:30]=2)[C:18]1=[O:50])=[O:15])C1C=CC=CC=1.Cl>CO.[Pd]>[OH:8][C@H:9]([CH3:53])[CH2:10][NH:11][C:12]([CH3:52])([CH3:51])[CH2:13][C:14]([NH:16][C@@H:17]1[CH2:23][CH2:22][C:21]2[CH:24]=[CH:25][CH:26]=[CH:27][C:20]=2[N:19]([CH2:28][C:29]2[CH:30]=[CH:31][C:32]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[CH2:41][NH:42][C:43]([O:45][C:46]([CH3:48])([CH3:47])[CH3:49])=[O:44])=[CH:33][CH:34]=2)[C:18]1=[O:50])=[O:15]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 228551463-[2(R)-Benzyloxypropyl]amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1-[[2'-[(t-butoxycarbonylamino)methyl][1,1'-biphenyl]-4-yl]methyl]-1H-benzazepin-3(R)-yl]butanamide

Product 1

HCID 228551493-[2(R)-Hydroxypropyl]amino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1-[[2'-[(t-butoxycarbonylamino)methyl][1,1'-biphenyl]-4-yl]methyl]-1H-benzazepin-3(R)-yl]butanamideYield 95%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of 525 mg (0.695 mmol) of the intermediate prepared in Step A in 6 mL of methanol was added 0.350 mL (0.700 mmol) of 2N hydrochloric acid and 100 mg (20% w/w) of 30% palladium on carbon. The resulting mixture was shaken under a hydrogen atmosphere at 40 psi for 24 hours. The catalyst was removed by filtration through Celite and the solvent removed under vacuum. The residue was purified by column flash chromatography on silica gel, eluting with chloroform/10% ammonium hydroxide in methanol (95/5), to give 415 mg (95%) of the product as a white solid. 1H NMR (400 MHz, CD3OD): δ1.12-1.21 (m, 9H), 1.42 (s, 9H), 2.04-2.13 (m, 1H), 2.22-2.41 (m, 3H), 2.49-2.62 (m, 4H), 3.80-3.88 (m, 1H), 4.09 (s, 2H), 4.42 (dd; 12, 4 Hz; 1H), 4.97 (d, 15 Hz, 1H), 5.30 (d, 15 Hz, 1H), 7.11-7.42 (m, 12 H). FAB-MS: calculated for C37H48N4O5 628; found 629 (M+H).

Workup

  1. customThe catalyst was removed by filtration through Celite
  2. customthe solvent removed under vacuum
  3. customThe residue was purified by column flash chromatography on silica gel
  4. washeluting with chloroform/10% ammonium hydroxide in methanol (95/5)

Sources & evidence

ORD record
ord-c3da6065a47341ceb1f2d23aaf6ca517
Source dataset
uspto-grants-1995_08
Patent number
US05438136

Reaction notes

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