4-Methylmorpholine → HCID 10007272, compound

HRID 2267638Notes

Reaction equation

HRID 2267638 reaction equation
[NH2:1][C@@H:2]1[C:8](=[O:9])[N:7]([CH2:10][CH:11]2[CH2:13][CH2:12]2)[C:6]2[CH:14]=[CH:15][CH:16]=[CH:17][C:5]=2[O:4][C@@H:3]1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[F:24][C:25]1[CH:26]=[C:27]([CH2:32][C:33]([NH:35][C@H:36]([C:38](O)=[O:39])[CH3:37])=[O:34])[CH:28]=[C:29]([F:31])[CH:30]=1.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.CCN=C=NCCCN(C)C.Cl>ClCCl>[CH:11]1([CH2:10][N:7]2[C:6]3[CH:14]=[CH:15][CH:16]=[CH:17][C:5]=3[O:4][C@H:3]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C@H:2]([NH:1][C:38](=[O:39])[C@H:36]([CH3:37])[NH:35][C:33](=[O:34])[CH2:32][C:27]3[CH:28]=[C:29]([F:31])[CH:30]=[C:25]([F:24])[CH:26]=3)[C:8]2=[O:9])[CH2:13][CH2:12]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 68607044HCID 68607044, compound

Product 1

HCID 10007272HCID 10007272, compoundYield 88.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (2R,3S)-3-amino-5-(cyclopropylmethyl)-2-phenyl-2,3-dihydro-1,5-benzoxazepin-4(5H)-one (72b) (150 mg, 0.486 mmol) in dichloromethane (4 mL) was added N-[(3,5-difluorophenyl)acetyl]-L-alanine (1e) (130 mg, 0.534 mmol), HOBt (75 mg, 0.555 mmol), NMM (60 mg, 0.594 mmol) and EDAC-HCl (103 mg, 0.537 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 flash chromatography on silica gel eluting with 5:1 (v/v) dichloromethane: ethyl acetate to afford the title compound (230 mg, 88%) as a white solid. TLC Rf=0.22 (5:1 dichloromethane:ethyl acetate). 1H NMR (300 MHz, CDCl3) δ0.20 (m, 1H), 0.36-0.64 (m, 3 h), 1.14 (m, 1H), 1.21 (d, 3H, J=7.0 Hz), 3.47 (s, 2H), 3.52 (m, 1H), 4.10-4.29 (m, 2H), 5.05 (t, 1-H, J=7.0 Hz), 5.68 (d, 1H, J=7.4 Hz), 5.90 (d, 1H), 6.24 (d, 1H), 6.68-6.85 (m, 3H), 7.28 (s, 4H), 7.36, s, 5H). MS APCI, m/z=534 (M+1). LC/MS: 2.78 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 5:1 (v/v) dichloromethane

Sources & evidence

ORD record
ord-ea6eed7cc61f458694c4ba6bfaeb3d3c
Source dataset
uspto-grants-2010_12
Patent number
US07858776B2

Reaction notes

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