Dimethylformamide → HCID 69939144, compound

HRID 1058272Notes

Reaction equation

HRID 1058272 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C:11]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:12]=1[CH2:13][NH:14][C:15](=[O:21])[C@@H:16]1[CH2:20][CH2:19][CH2:18][NH:17]1)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1[CH2:33][CH2:32][O:31]CC1.CN([P+](ON1N=N[C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][C:46]1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.CN(C=[O:65])C>>[OH:65][C@H:33]([CH:46]1[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]1)[C:32]([N:17]1[CH2:18][CH2:19][CH2:20][C@H:16]1[C:15]([NH:14][CH2:13][C:12]1[CH:22]=[C:23]([Cl:26])[CH:24]=[CH:25][C:11]=1[CH:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH3:10])=[O:21])=[O:31]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 23560072HCID 23560072, compound

Product 1

HCID 69939144HCID 69939144, compound

Procedure

To a stirred solution of L-prolin-N-(2-(1-(tert-butyloxycarbonylamino)ethyl)-5-chlorobenzyl)amide from the previous step (75 mg, 0.196 mmol), R-(−)-hexahydro-mandelic acid(34.2 mg, 0.22 mmol), and NMM (22 μL, 0.196 mmol) in DMF (5 mL) at ambient temperature under nitrogen atmosphere was added BOP reagent (104 mg, 0.24 mmol). The mixture was stirred at ambient temperature for 5 h. The solvent was removed under reduced pressure and the residue was purified by preparative thick layer silica gel plate chromatography (2000 μM×20 cm×20 cm) developed with 7.5% MeOH in dichloromethane. Desired bands were removed and eluted with 5% MeOH in dichloromethane which were concentrated in vacuo to obtain 1-((2R)-2-hydroxy-2-cyclohexylethanoyl)-N-(2-(1-(tert-butyloxycarbonylamino)ethyl)-5-chlorobenzyl)-L-prolinamide as a clear colorless oil (85 mg; HPLC RT 3.51 min, method A; LC-MS m/z=522.2).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue was purified by preparative thick layer silica gel plate chromatography (2000 μM×20 cm×20 cm)
  3. customDesired bands were removed
  4. washeluted with 5% MeOH in dichloromethane which
  5. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-e0beec286ad5415f858fe65214cd01f3
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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