Tris(hydroxymethyl)aminomethane → N-[(1S,2S,4R)-1-Benzyl-4-(3,3-dimethylbutylcarbamoyl)-2-hydroxypentyl]-3-(2-oxopyrrolidin-1-yl)-5-phenylbenzamide

HRID 1612479Notes

Reaction equation

HRID 1612479 reaction equation
N=C=N.C1C=CC2N(O)N=NC=2C=1.[O:14]=[C:15]1[CH2:19][CH2:18][CH2:17][N:16]1[C:20]1[CH:21]=[C:22]([C:32](O)=[O:33])[CH:23]=[C:24]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:25]=1.[CH3:35][C:36]([CH3:57])([CH3:56])[CH2:37][CH2:38][NH:39][C:40](=[O:55])[C@H:41]([CH3:54])[CH2:42][C@H:43]([OH:53])[C@@H:44]([NH2:52])[CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.C(O)C(N)(CO)CO.[N-]=C=O>C(Cl)Cl.CN(C=O)C.C(Cl)Cl>[CH2:45]([C@H:44]([NH:52][C:32](=[O:33])[C:22]1[CH:23]=[C:24]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:25]=[C:20]([N:16]2[CH2:17][CH2:18][CH2:19][C:15]2=[O:14])[CH:21]=1)[C@@H:43]([OH:53])[CH2:42][C@H:41]([C:40](=[O:55])[NH:39][CH2:38][CH2:37][C:36]([CH3:56])([CH3:35])[CH3:57])[CH3:54])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1

Participants

9

Reactant 6

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 757711-HydroxybenzotriazoleHCID 105034IsocyanateHCID 160435CarbodiimideHCID 222529945-(2-Oxopyrrolidin-1-yl)-biphenyl-3-carboxylic AcidHCID 68890142(2R,4S,5S)-5-amino-4-hydroxy-2-methyl-6-phenylhexanoic acid (3,3-dimethylbutyl)-amide

Product 1

HCID 10129098N-[(1S,2S,4R)-1-Benzyl-4-(3,3-dimethylbutylcarbamoyl)-2-hydroxypentyl]-3-(2-oxopyrrolidin-1-yl)-5-phenylbenzamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent2×

Procedure

Polystyrene linked carbodiimide (21 mg, 1.7 mmol/g, 0.036 mmol) was placed in a vial with DCM (1 ml). To this was added HOBT (5 mg, 0.036 mmol) in 1 ml DCM/DMF=4:1, 5-(2-oxo-pyrrolidin-1-yl)-biphenyl-3-carboxylic acid (D11) (10 mg, 0.036 mmol) in 1 ml DCM/DMF=4:1, and (2R,4S,5S)-5-amino-4-hydroxy-2-methyl-6-phenylhexanoic acid (3,3-dimethylbutyl)amide (D2) (in 1 ml DCM). The mixture was stirred at room temperature overnight. Scavenger resins trisamine (˜100 mg) and isocyanate (˜100 mg) were added and the mixture was stirred for another 1.5 hours. The resins were filtered and the solvent evaporated in vacuo. Column chromatography on silica gel (5% MeOH in DCM) gave E6 (5 mg).

Workup

  1. stirringthe mixture was stirred for another 1.5 hours
  2. filtrationThe resins were filtered
  3. customthe solvent evaporated in vacuo

Sources & evidence

ORD record
ord-57cf193524084a2cb1c08697fd036056
Source dataset
uspto-grants-2006_01
Patent number
US06992103B2

Reaction notes

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