4-Methylmorpholine → HCID 10413450, compound

HRID 1392098Notes

Reaction equation

HRID 1392098 reaction equation
[NH2:1][C@@H:2]1[CH2:8][CH:7]=[CH:6][C@@H:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:4]([CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[C:3]1=[O:20].[F:21][C:22]1[CH:23]=[C:24]([CH2:29][C:30]([NH:32][C@H:33]([C:35](O)=[O:36])[CH3:34])=[O:31])[CH:25]=[C:26]([F:28])[CH:27]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.CN1CCOCC1>C(Cl)Cl>[CH:15]1([N:4]2[C@H:5]([C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:6]=[CH:7][CH2:8][C@@H:2]([NH:1][C:35](=[O:36])[C@H:33]([CH3:34])[NH:32][C:30](=[O:31])[CH2:29][C:24]3[CH:25]=[C:26]([F:28])[CH:27]=[C:22]([F:21])[CH:23]=3)[C:3]2=[O:20])[CH2:19][CH2:18][CH2:17][CH2:16]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 58691171HCID 58691171, compound

Product 1

HCID 10413450HCID 10413450, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (3R,7S)-3-amino-1-cyclopentyl-7-phenyl-1,3,4,7-tetrahydro-2H-azepin-2-one (8f) (65 mg) in DCM (4 ml) at RT under N2 was added N-[(3,5-difluorophenyl)acetyl]-L-alanine (59 mg), HOBt (65 mg), EDAC.HCl (69 mg), and N-methylmorpholine (24 mg). The reaction was stirred at RT overnight, then diluted with DCM (10 ml) and washed with 1N HCl, 1N K2CO3, dried (Na2SO4), filtered and evaporated. The crude product was purified by flash chromatography (2% MeOH/DCM) to afford the title compound as an off white solid (60 mg, 50%). 1H NMR (300 MHz, CDCl3) δ 1.28 (d, 3H, J=7 Hz), 1.37-1.70 (m, 6H), 1.94-2.16 (m, 3H), 2.50-2.60 (m, 1H), 3.48 (s, 2H), 4.36-4.55 (m, 2H), 4.96 (d, 1H, J=8 Hz), 5.20 (tt, 1H, J=9 Hz, J=9 Hz), 5.87-5.94 (m, 1H), 6.18-6.33 (m, 2H), 6.67-6.80 (m, 3H), 7.00 (d, 1H, J=6 Hz), 7.25-7.38 (m, 5H). MS APCI, m/z=496 (M+1), LC/MS, 2.54 min.

Workup

  1. washwashed with 1N HCl, 1N K2CO3
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. customevaporated
  5. customThe crude product was purified by flash chromatography (2% MeOH/DCM)

Sources & evidence

ORD record
ord-963c2b9b7b884381ba765b85ec9f78e4
Source dataset
uspto-grants-2008_03
Patent number
US07342007B2

Reaction notes

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