4-Methylmorpholine → HCID 68606807, compound

HRID 2267627Notes

Reaction equation

HRID 2267627 reaction equation
[NH2:1][C@@H:2]([C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1)[C:3]([NH:5][C@@H:6]1[C:12](=[O:13])[NH:11][C:10]2[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=2[O:8][C@@H:7]1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:4].[CH:31]1([CH2:37][C:38](O)=[O:39])[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.CCN=C=NCCCN(C)C.Cl>ClCCl>[CH:31]1([CH2:37][C:38]([NH:1][C@@H:2]([C:24]2[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=2)[C:3]([NH:5][C@@H:6]2[C:12](=[O:13])[NH:11][C:10]3[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=3[O:8][C@@H:7]2[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:4])=[O:39])[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 21363Cyclohexaneacetic acidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68604780HCID 68604780, compound

Product 1

HCID 68606807HCID 68606807, compoundYield 84.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (2S)-2-amino-2-(4-fluorophenyl)-N-[(2R,3S)-4-oxo-2-phenyl-2,3,4,5-tetrahydro-1,5-benzoxazepin-3-yl]acetamide (65b) (81 mg, 0.199 mmol) in dichloromethane (2 mL) under nitrogen was added cyclohexylacetic acid (35 mg, 0.246 mmol), HOBt (35 mg, 0.259 mmol), NMM (30 mg, 0.297 mmol) and EDAC-HCl (50 mg, 0.261 mmol). The mixture was stirred 5 h at ambient temperature then evaporated. The residue was dissolved in ethyl acetate and extracted in succession with saturated sodium bicarbonate, 1N aqueous HCl, and brine. The organic solution was dried, filtered and evaporated. The residue was purified by flash chromatography on silica gel eluting with 6:1 (v/v) dichloromethane:ethyl acetate to afford the title compound (89 mg, 84%) as a white solid. TLC Rf=0.42 (6:1 dichloromethane:ethyl acetate). 1H NMR (300 MHz, CDCl3) δ0.81-1.37 (m, 5H), 1.59-1.87 (m, 6H), 2.09 (d, 2H, J=6.5 Hz), 5.09 (t, 1H, J=7.0 Hz), 5.26 (d, 1H, J=7.0 Hz), 5.83 (d, 1H, J=7.0 Hz), 6.24 (br d, 1H, J=6.5 Hz), 6.48 (br d, 1H, J=6.5 Hz), 6.88-7.05 (m, 3H), 7.12-7.30 (m, 5H), 7.36 (s, 5H), 7.56 (br s, 1H). MS APCI, m/z=530 (M+1). LC/MS: 2.69 min.

Workup

  1. customthen evaporated
  2. dissolutionThe residue was dissolved in ethyl acetate
  3. extractionextracted in succession with saturated sodium bicarbonate, 1N aqueous HCl, and brine
  4. customThe organic solution was dried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by flash chromatography on silica gel eluting with 6:1 (v/v) dichloromethane

Sources & evidence

ORD record
ord-95ebd060759e459aba929c7cbec8c504
Source dataset
uspto-grants-2010_12
Patent number
US07858776B2

Reaction notes

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