Trifluoroacetic acid → 3-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[2,3,4,5-tetrahydro-1-[[2'-[[[(methyl-amino)carbonyl]amino]methyl][1,1'-biphenyl]-4-yl]methyl]-2-oxo-1H-benzazepin-3(R)-yl]butanamide

HRID 1740241Notes

Reaction equation

HRID 1740241 reaction equation
CC1(C)[O:6][C@@H:5]([CH2:7][NH:8][C:9]([CH3:46])([CH3:45])[CH2:10][C:11]([NH:13][C@@H:14]2[CH2:20][CH2:19][C:18]3[CH:21]=[CH:22][CH:23]=[CH:24][C:17]=3[N:16]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=4[CH2:38][NH:39][C:40]([NH:42][CH3:43])=[O:41])=[CH:28][CH:27]=3)[C:15]2=[O:44])=[O:12])[CH2:4][O:3]1.FC(F)(F)C(O)=O>CO>[OH:6][C@H:5]([CH2:4][OH:3])[CH2:7][NH:8][C:9]([CH3:45])([CH3:46])[CH2:10][C:11]([NH:13][C@@H:14]1[CH2:20][CH2:19][C:18]2[CH:21]=[CH:22][CH:23]=[CH:24][C:17]=2[N:16]([CH2:25][C:26]2[CH:27]=[CH:28][C:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[CH2:38][NH:39][C:40]([NH:42][CH3:43])=[O:41])=[CH:30][CH:31]=2)[C:15]1=[O:44])=[O:12]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 228774533-[[2,2-Dimethyl-1,3-dioxolan-4(S)-yl]methyl]amino-3-methyl-N-[2,3,4,5-tetrahydro-1-[[2'-[[[(methylamino)carbonyl]amino]methyl][1,1'-biphenyl]-4-yl]methyl]-2-oxo-1H-benzazepin-3(R)-yl]butanamide

Product 1

HCID 228773043-[2(S),3-Dihydroxypropyl]amino-3-methyl-N-[2,3,4,5-tetrahydro-1-[[2'-[[[(methyl-amino)carbonyl]amino]methyl][1,1'-biphenyl]-4-yl]methyl]-2-oxo-1H-benzazepin-3(R)-yl]butanamideYield 84.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 137 mg (0.213 mmol) of 3-[[2,2-dimethyl-1,3-dioxolan-4(S)-yl]methyl]amino-3-methyl-N-[2,3,4,5-tetrahydro-1-[[2'-[[[(methylamino)carbonyl]amino]methyl][1,1'-biphenyl]-4-yl]-methyl]-2-oxo-1H-benzazepin-3(R)-yl]butanamide (Step C) in 2 mL of methanol was added 2.0 mL of 50% aqueous trifluoroacetic acid. The resulting solution was stirred at room temperature for 3 hours at which time the solvent was removed under vacuum to give a solid which was purified by reverse phase medium pressure liquid chromatography on C-8, eluting with methanol/0.1% aqueous trifluoroacetic acid (55:45), to afford 108 mg (70%) of the title compound as a white solid. 1H NMR (200 MHz, CD3OD): δ 1.35 (s, 3H), 1.37 (s, 3H), 2.02-2.22 (m, 1H), 2.22-2.43 (m, 1H), 2.50-2.70 (m,4H), 2.64 (s,3H), 2.94 (dd, 12, 9 Hz; 1H), 3.17 (dd, 12, 3 Hz; 1H), 3.51 (m, 2H), 3.82 (m, 1H), 4.16 (s, 2H), 4.38 (dd, 12, 8 Hz; 1H), 5.03 (d, 15 Hz, 1H), 5.14 (d, 15 Hz, 1H), 7.10-7.40 (m, 12H). FAB-MS: calculated for C34H43N5O5 601; found 602 (M+H, 40%).

Workup

  1. customwas removed under vacuum
  2. customto give a solid which
  3. customwas purified by reverse phase medium pressure liquid chromatography on C-8
  4. washeluting with methanol/0.1% aqueous trifluoroacetic acid (55:45)

Sources & evidence

ORD record
ord-8f1075ca5cf448039ee2739b58b8d60e
Source dataset
uspto-grants-1999_10
Patent number
US05968924

Reaction notes

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