N-((1,1-dimethylethoxy)carbonyl)-beta-alanine → 3-t-Butoxycarbonylamino-N-[2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3-yl]-propanamide

HRID 1591425Notes

Reaction equation

HRID 1591425 reaction equation
[NH2:1][CH:2]1[CH2:8][CH2:7][C:6]2[CH:9]=[CH:10][CH:11]=[CH:12][C:5]=2[NH:4][C:3]1=[O:13].[C:14]([O:18][C:19]([NH:21][CH2:22][CH2:23][C:24](O)=[O:25])=[O:20])([CH3:17])([CH3:16])[CH3:15].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl.C(OCC)(=O)C>[C:14]([O:18][C:19]([NH:21][CH2:22][CH2:23][C:24]([NH:1][CH:2]1[CH2:8][CH2:7][C:6]2[CH:9]=[CH:10][CH:11]=[CH:12][C:5]=2[NH:4][C:3]1=[O:13])=[O:25])=[O:20])([CH3:17])([CH3:16])[CH3:15]

Participants

7

Reactant 4

HCID 76809N-((1,1-dimethylethoxy)carbonyl)-beta-alanineHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 44344333-Amino-2,3,4,5-tetrahydro-1H-benzazepin-2-one

Product 1

HCID 190255583-t-Butoxycarbonylamino-N-[2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3-yl]-propanamideYield 78.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 50 mg (0.28 mmol) 3-amino-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (Example 1; Step A) in 2 mL methylene chloride at room temperature was added 56 mg (0.30 mmol, 1.05 eq) 3-(t-butoxycarbonylamino)propanoic acid followed by 0.1 mL diisopropylethylamine (74 mg, 0.57 mmol, 2 eq) and 190 mg (0.43 mmol, 1.5 eq) benzotriazol-1-yloxytris(dimethylamino) phosphonium hexafluorophosphate. After 1 hour at room temperature, the mixture was added to 20 mL ethyl acetate and washed with 1M aqueous citric acid, saturated aqueous sodium bicarbonate and brine. The organic layer was removed, dried over magnesium sulfate, filtered and solvents removed in vacuo. The residue was purified by medium pressure liquid chromatography on silica, eluting with ethyl acetate/hexane (2:1) to afford 76 mg (0.22 mmol, 77%) of product as a white solid. 1H NMR (200 MHz, CDCl3): 1.40 (s,9H), 1.95 (m,1H), 2.40 (t,6 Hz,2H), 2.6-3.0 (m,3H), 3.36 (q,6 Hz, 2H), 4.52 (m,1H), 5.15 (br t,1H), 6.58 (br d,1H), 7.0-7.3 (m,4H), 7.6 (br s,1H). FAB-MS: calc. for C18H25N3O4 347; found 348 (M+H,35%).

Workup

  1. washwashed with 1M aqueous citric acid, saturated aqueous sodium bicarbonate and brine
  2. customThe organic layer was removed
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. customsolvents removed in vacuo
  6. customThe residue was purified by medium pressure liquid chromatography on silica
  7. washeluting with ethyl acetate/hexane (2:1)

Sources & evidence

ORD record
ord-eb7db22a378e4f47a37efc94fc27e9f7
Source dataset
uspto-grants-1993_04
Patent number
US05206235

Reaction notes

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