4-Methylmorpholine → HCID 10324158, compound

HRID 1392111Notes

Reaction equation

HRID 1392111 reaction equation
[NH2:1][C@H:2]1[CH2:8][CH:7]=[CH:6][C@@H:5]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2)[N:4]([CH2:17][CH:18]2[CH2:20][CH2:19]2)[C:3]1=[O:21].[OH:22][C@@H:23]([CH2:35][CH:36]([CH3:38])[CH3:37])[C:24]([NH:26][C@H:27]([C:32](O)=[O:33])[CH2:28][CH:29]([CH3:31])[CH3:30])=[O:25].CCN=C=NCCCN(C)C.Cl.CN1CCOCC1>C(Cl)Cl>[CH:18]1([CH2:17][N:4]2[C@H:5]([C:9]3[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=3)[CH:6]=[CH:7][CH2:8][C@H:2]([NH:1][C:32](=[O:33])[C@H:27]([CH2:28][CH:29]([CH3:31])[CH3:30])[NH:26][C:24](=[O:25])[C@@H:23]([OH:22])[CH2:35][CH:36]([CH3:37])[CH3:38])[C:3]2=[O:21])[CH2:19][CH2:20]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58691169HCID 58691169, compoundHCID 58691191HCID 58691191, compound

Product 1

HCID 10324158HCID 10324158, compoundYield 95.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (3S,7S)-3-amino-1-(cyclopylmethyl)-7-(4-methoxyphenyl)-1,3,4,7-tetrahydro-2H-azepin-2-one (11e) (35 mg) in DCM (3 mL) at 0° C. under N2 was added N-[(2S)-2-hydroxy-4-methylpentanoyl]-L-leucine (7b) (30 mg), HOBt-hydrate (41 mg), EDAC.HCl (35 mg) and N-methyl morpholine (25 mg). The reaction mixture was stirred 1 h at 0° C. and 3H at room temperature, then diluted with 30% Hexanes/EtOAc (100 mL). The organic phase was consecutively washed with H2O, 0.2 N HCl, saturated NaHCO3, and brine, 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, 95%). 1H NMR (300 MHz, CDCl3) δ 0.40 (m, 2H), 0.58 (m, 2H), 0.74 (m, 1H), 0.87 (d, 6H), 1.26 (m, 1H), 1.53, (m, 2H), 1.59 (m, 1H), 1.67 (m, 2H), 2.00 (m, 2H), 3.20 (m, 2H), 3.66 (s, 1H), 3.89 (m, 1H), 4.28 (m, 1H), 4.96 (m, 1H), 5.32 (m, 1H), 6.13 (bd, 1H), 6.48 (m, 1H), 6.85-6.94 (m, 4H). MS APCI, m/z=514 (M+1). LC/MS 2.47 min., Method A.

Workup

  1. washThe organic phase was consecutively washed with H2O, 0.2 N HCl, saturated NaHCO3, and brine
  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-db449550855a4826bc1d1b07d733e0b6
Source dataset
uspto-grants-2008_03
Patent number
US07342007B2

Reaction notes

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