1,2-Dichloroethane → N-[(2S)-2-({3-[(dipropylamino)carbonyl]-benzoyl}amino)-3-phenylpropyl]-L-alanyl-N1-isobutyl-L-valinamide

HRID 1062894Notes

Reaction equation

HRID 1062894 reaction equation
[CH2:1]([N:4]([CH2:16][CH2:17][CH3:18])[C:5]([C:7]1[CH:8]=[C:9]([CH:13]=[CH:14][CH:15]=1)[C:10]([OH:12])=O)=[O:6])[CH2:2][CH3:3].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[NH2:33][C@@H:34]([CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)[CH2:35][NH:36][C@H:37]([C:39]([NH:41][C@H:42]([C:46]([NH:48][CH2:49][CH:50]([CH3:52])[CH3:51])=[O:47])[CH:43]([CH3:45])[CH3:44])=[O:40])[CH3:38]>CN(C=O)C>[CH2:16]([N:4]([CH2:1][CH2:2][CH3:3])[C:5]([C:7]1[CH:8]=[C:9]([CH:13]=[CH:14][CH:15]=1)[C:10]([NH:33][C@@H:34]([CH2:53][C:54]1[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=1)[CH2:35][NH:36][C@H:37]([C:39]([NH:41][C@H:42]([C:46]([NH:48][CH2:49][CH:50]([CH3:51])[CH3:52])=[O:47])[CH:43]([CH3:44])[CH3:45])=[O:40])[CH3:38])=[O:12])=[O:6])[CH2:17][CH3:18]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 1827693-(Dipropylcarbamoyl)benzoic acidHCID 69735335N-[(2S)-2-amino-3-phenylpropyl]-L-alanyl-N1-isobutyl-L-valinamide

Product 1

HCID 9938756N-[(2S)-2-({3-[(dipropylamino)carbonyl]-benzoyl}amino)-3-phenylpropyl]-L-alanyl-N1-isobutyl-L-valinamideYield 51.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

3-[(Dipropylamino)carbonyl]benzoic acid, (52 mg, 0.21 mmol) is combined with EDC(40 mg, 0.21 mmol) and HOBT (30 mg, 0.22 mmol) in 2.5 mL of DMF and stirred under nitrogen for 1 h. This solution is then added to a solution of N-[(2S)-2-amino-3-phenylpropyl]-L-alanyl-N1-isobutyl-L-valinamide (0.17 mmol) in 1 mL of DMF. The reaction is continued for 3 days at ambient temperature. It is then quenched with 1 N KH2PO4 and diluted with ethyl acetate. The organic phase is washed with water, 1 N NaHCO3, and brine, and dried over Na2SO4. Concentration and chromatography over silica gel, eluting with 5% methanol in dichloromethane, affords 53 mg (0.087 mmol, 51%) of the title compound. Addition of several drops of deuterated methanol to the compound in deuterated chloroform is necessary. NMR (CDCl3+MeOD) δ 7.79 (br d, 1H), 7.69 (s, 1H), 7.44 (m, 2H), 7.30 (m, 4H), 7.26 (m, obscured by CHCl3), 7.19 (m, 2H), 4.33 (m, 1H), 4.03 (d, J=8 Hz, 1H), 3.5-3.4 (m, 3H), 3.13-3.0 (m, 6H), 2.90 (m, 1H), 2.68 (dd, 1H), 2.0 (m, 1H), 1.8-1.7 (m, 3H), 1.5 (m, 2H), 1.31 (d, J=7 Hz, 3H), 0.99 (t, J=7 Hz, 3H), 0.93-0.86 (overlapping d, 12H), 0.72 (t, J=7 Hz, 3H). MS (FAB) m/z 608 (MH+).

Workup

  1. waitThe reaction is continued for 3 days at ambient temperature
  2. customIt is then quenched with 1 N KH2PO4
  3. additiondiluted with ethyl acetate
  4. washThe organic phase is washed with water, 1 N NaHCO3, and brine
  5. dry with materialdried over Na2SO4
  6. concentrationConcentration and chromatography over silica gel
  7. washeluting with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-edeab5b90374461a9fb66e21075f4b5d
Source dataset
uspto-grants-2005_11
Patent number
US06962934B2

Reaction notes

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