4-Methylmorpholine → N2-[(3,5-Difluorophenyl)acetyl]-N1-[(2R,3S)-4-oxo-2-phenyl-5-prop-2-yn-1-yl-2,3,4,5-tetrahydro-1,5-benzoxazepin-3-yl]-L-alaninamide

HRID 1593291Notes

Reaction equation

HRID 1593291 reaction equation
[NH2:1][C@@H:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]#[CH:12])[C:6]2[CH:13]=[CH:14][CH:15]=[CH:16][C:5]=2[O:4][C@@H:3]1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[F:23][C:24]1[CH:25]=[C:26]([CH2:31][C:32]([NH:34][C@H:35]([C:37](O)=[O:38])[CH3:36])=[O:33])[CH:27]=[C:28]([F:30])[CH:29]=1.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.CCN=C=NCCCN(C)C.Cl>ClCCl>[F:23][C:24]1[CH:25]=[C:26]([CH2:31][C:32]([NH:34][C@H:35]([C:37]([NH:1][C@@H:2]2[C:8](=[O:9])[N:7]([CH2:10][C:11]#[CH:12])[C:6]3[CH:13]=[CH:14][CH:15]=[CH:16][C:5]=3[O:4][C@@H:3]2[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:38])[CH3:36])=[O:33])[CH:27]=[C:28]([F:30])[CH:29]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 12135350(2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]propanoic acidHCID 86604636HCID 86604636, compound

Product 1

HCID 86604635N2-[(3,5-Difluorophenyl)acetyl]-N1-[(2R,3S)-4-oxo-2-phenyl-5-prop-2-yn-1-yl-2,3,4,5-tetrahydro-1,5-benzoxazepin-3-yl]-L-alaninamideYield 74.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (2R,3S)-3-amino-2-phenyl-5-prop-2-yn-1-yl-2,3-dihydro-1,5-benzoxazepin-4(5H)-one (67c) (65 mg, 0.222 mmol) in dichloromethane (3 mL) was added N-[(3,5-difluorophenyl)acetyl]-L-alanine (1e) (65 mg, 0.267 mmol), HOBt (40 mg, 0.296 mmol), NMM (31 mg, 0.306 mmol) and EDAC-HCl (55 mg, 0.286 mmol). After stirring at ambient temperature under nitrogen overnight the solvent was evaporated and the residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic solution was separated, washed with 1N aqueous HCl then dried, filtered and evaporated. The residue was purified by recrystallization from 1:1 (v/v) ethyl acetate:hexanes to afford the title compound (86 mg, 74%) as a white solid. TLC Rf=0.25 (diethyl ether). 1H NMR (300 MHz, CDCl3) δ1.22 (d, 3H, J=7.0 Hz), 2.31 (m, 1H), 3.48 (s, 2H), 4.23 (m, 1H), 4.69 (d, 2H, J=2.2 Hz), 5.11 (t, 1H, J=7.0 Hz), 5.69 (d, 1H, J=7.4 Hz), 5.87 (d, 1H), 6.18 (d, 1H), 6.69-6.86 (m, 3H), 7.26-7.53 (m, 9H). MS APCI, m/z=518 (M+1). LC/MS: 2.63 min.

Workup

  1. customwas evaporated
  2. customthe residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate
  3. customThe organic solution was separated
  4. washwashed with 1N aqueous HCl
  5. customthen dried
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by recrystallization from 1:1 (v/v) ethyl acetate

Sources & evidence

ORD record
ord-060eb2039d4c4a4096b681e2339c6d73
Source dataset
uspto-grants-2007_11
Patent number
US07294622B2

Reaction notes

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