4-Methylmorpholine → HCID 10007272, compound

HRID 1593300Notes

Reaction equation

HRID 1593300 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, 1H, 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-b654fa3abc5749b982cf883a05772592
Source dataset
uspto-grants-2007_11
Patent number
US07294622B2

Reaction notes

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