4-Methylmorpholine → HCID 86604639, compound

HRID 1593296Notes

Reaction equation

HRID 1593296 reaction equation
[NH2:1][C@@H:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([O:13][CH3:14])=[O:12])[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[O:4][C@@H:3]1[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[F:25][C:26]1[CH:27]=[C:28]([CH2:33][C:34]([NH:36][C@H:37]([C:39](O)=[O:40])[CH3:38])=[O:35])[CH:29]=[C:30]([F:32])[CH:31]=1.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.CCN=C=NCCCN(C)C.Cl>ClCCl>[F:25][C:26]1[CH:27]=[C:28]([CH2:33][C:34]([NH:36][C@H:37]([C:39]([NH:1][C@@H:2]2[C:8](=[O:9])[N:7]([CH2:10][C:11]([O:13][CH3:14])=[O:12])[C:6]3[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=3[O:4][C@@H:3]2[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:40])[CH3:38])=[O:35])[CH:29]=[C:30]([F:32])[CH:31]=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 59863953HCID 59863953, compound

Product 1

HCID 86604639HCID 86604639, compoundYield 84.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of methyl [(2R,3S)-3-amino-4-oxo-2-phenyl-3,4-dihydro-1,5-benzoxazepin-5(2H)-yl]acetate (70b) (130 mg, 0.398 mmol) in dichloromethane (4 mL) was added N-[(3,5-difluorophenyl)acetyl]-L-alanine (1e) (125 mg, 0.514 mmol), HOBt (71 mg, 0.525 mmol), NMM (53 mg, 0.525 mmol) and EDAC-HCl (100 mg, 0.522 mmol). After stirring at ambient temperature under nitrogen for 48 h 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 flash chromatography on silica gel eluting with 1:1 (v/v) hexane:ethyl acetate to afford the title compound (185 mg, 82%) as a white solid. TLC Rf=0.13 (1:1 hexane:ethyl acetate). 1H NMR (300 MHz, CDCl3) δ1.21 (d, 3H, J=7.0 Hz), 3.46 (s, 2H), 3.80 (s, 3H), 4.23 (m, 1H), 4.55 and 4.68 (AB quartet, 2H, J=17.1 Hz), 5.16 (t, 1H, J=7.2 Hz), 5.72 (d, 1H, J=7.4 Hz), 5.87 (br d, 1H, J=7.0 Hz), 6.17 (br d, 1H, J=6.6 Hz), 6.66-6.87 (m, 3H), 7.19-7.33 (m, 4H), 7.37 (s, 5H). MS APCI, m/z=552 (M+1). LC/MS: 2.52 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 flash chromatography on silica gel eluting with 1:1 (v/v) hexane

Sources & evidence

ORD record
ord-a20c6ab031a648199c3f1597a681ee50
Source dataset
uspto-grants-2007_11
Patent number
US07294622B2

Reaction notes

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