Diisopropylethylamine → 4-[[(4-cyano-4-phenyl-1-piperidinyl)carbonyl]amino]-N-[(2,2-dichloro-1-methylcyclopropyl)carbonyl]-L-phenylalanine

HRID 393442

Reaction equation

HRID 393442 reaction equation
[C:1]([C:3]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:8][CH2:7][N:6]([C:9]([NH:11][C:12]2[CH:23]=[CH:22][C:15]([CH2:16][C@@H:17]([C:19]([OH:21])=[O:20])[NH2:18])=[CH:14][CH:13]=2)=[O:10])[CH2:5][CH2:4]1)#[N:2].[Cl:30][C:31]1([Cl:38])[CH2:33][C:32]1([CH3:37])[C:34](O)=[O:35].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CN1CCCC1=O>[C:1]([C:3]1([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:8][CH2:7][N:6]([C:9]([NH:11][C:12]2[CH:23]=[CH:22][C:15]([CH2:16][C@@H:17]([C:19]([OH:21])=[O:20])[NH:18][C:34]([C:32]3([CH3:37])[CH2:33][C:31]3([Cl:38])[Cl:30])=[O:35])=[CH:14][CH:13]=2)=[O:10])[CH2:5][CH2:4]1)#[N:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 1026212,2-Dichloro-1-methylcyclopropanecarboxylic acidHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 539777144-[[(4-cyano-4-phenyl-1-piperidinyl)carbonyl]amino]-L-phenylalanine

Product 1

HCID 571258534-[[(4-cyano-4-phenyl-1-piperidinyl)carbonyl]amino]-N-[(2,2-dichloro-1-methylcyclopropyl)carbonyl]-L-phenylalanine

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A suspension of 4-[[(4-cyano-4-phenyl-1-piperidinyl)carbonyl]amino]-L-phenylalanine on Wang resin (0.30 g, 0.228 mmol), 2,2-dichloro-1-methylcyclopropane carboxylic acid (0.19 g, 1.14 mmol), BOP (0.50 g, 1.14 mmol) and DIPEA (0.26 mL, 1.5 mmol) in N-methylpyrrolidinone (3 mL) was agitated for 3 hr. The mixture was filtered and washed with dichloromethane and methanol. Cleavage from the resin was effected by treatment with 90% TFA in dichloromethane for 3 min. The mixture was filtered and the filtrate evaporated to give 4-[[(4-cyano-4-phenyl-1-piperidinyl)carbonyl]amino]-N-[(2,2-dichloro-1-methylcyclopropyl)carbonyl]-L-phenylalanine. FAB MS m/z 543 (M+H).

Workup

  1. filtrationThe mixture was filtered
  2. washwashed with dichloromethane and methanol
  3. waitCleavage from the resin was effected by treatment with 90% TFA in dichloromethane for 3 min
  4. filtrationThe mixture was filtered
  5. customthe filtrate evaporated

Sources & evidence

ORD record
ord-f7012c36992b49ada743a4b148da1dc5
Source dataset
uspto-grants-2004_10
Patent number
US06806365B2

Linked notes

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