4-Methylmorpholine → HCID 10051473, compound

HRID 1392099Notes

Reaction equation

HRID 1392099 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]([OH:37])=[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.[CH:15]1([N:4]2[C@@H:5]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH:6]=[CH:7][CH2:8][C@@H:2]([NH:1][C:35](=[O:37])[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])[CH2:16][CH2:17][CH2:18][CH2:19]1

Participants

8

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 58691206HCID 58691206, compound

Product 2

HCID 10051473HCID 10051473, compoundHCID 69208942HCID 69208942, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of crude (3S,7S)-3-amino-1-cyclopentyl-7-phenyl-1,3,4,7-tetrahydro-2H-azepin-2-one (8d) (40 mg) in DCM (3 ml) at RT under N2 was added N-[(3,5-difluorophenyl)acetyl]-L-alanine (36 mg), HOBt (40 mg), EDAC.HCl (42 mg), and N-methylmorpholine (15 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 a 70:30 mixture with N1-[(3R,7R)-1-cyclopentyl-2-oxo-7-phenyl-2,3,4,7-tetrahydro-1H-azepin-3-yl]-N2-[(3,5-difluorophenyl)acetyl]-L-alaninamide as an off white solid (55 mg, 75%). 1H NMR (300 MHz, CDCl3) δ 1.17-2.21 (m, 12H), 2.79-2.87 (m, 1H), 3.55 (s, 2H), 5.44-5.52 (m, 1H), 5.80-5.84 (m, 1H), 5.90-5.93 (s, 1H), 6.26-6.35 (m, 2H), 6.69-6.86 (m, 3H), 7.19-7.46-(m, 6H). MS APCI, m/z=496 (M+1), LC/MS, 2.65 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-4875210fe4b34dcc8ac7a297d9368a4e
Source dataset
uspto-grants-2008_03
Patent number
US07342007B2

Reaction notes

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