Nicotinic Acid → n-((1r)-1-[(4-Chlorophenyl)methyl]-2-oxo-2-{4-[2-(3-pyridylcarbonylamino)phenyl]piperazinyl}ethyl)((3s)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide

HRID 1242755Notes

Reaction equation

HRID 1242755 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:33][C:34]([C@@H:36]2[CH2:45][C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[CH2:38][N:37]2C(OC(C)(C)C)=O)=[O:35])[C:10](=[O:32])[N:11]2[CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[NH:23][C:24]([C:26]3[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=3)=[O:25])[CH2:13][CH2:12]2)=[CH:4][CH:3]=1.NC1C=CC=CC=1N1CCN(C(=O)[C@H](NC([C@@H]2CC3C(=CC=CC=3)CN2C(OC(C)(C)C)=O)=O)CC2C=CC(Cl)=CC=2)CC1.C(O)(=O)C1C=CC=NC=1.C1C=NC2N(O)N=NC=2C=1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C@@H:9]([NH:33][C:34]([C@@H:36]2[CH2:45][C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[CH2:38][NH:37]2)=[O:35])[C:10](=[O:32])[N:11]2[CH2:12][CH2:13][N:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[NH:23][C:24]([C:26]3[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=3)=[O:25])[CH2:15][CH2:16]2)=[CH:6][CH:7]=1

Participants

5

Reactant 4

HCID 938Nicotinic AcidHCID 181649HOAtHCID 58714321tert-butyl 3-(N-{(1R)-2-[4-(2-aminophenyl)piperazinyl]-1-[(4-chlorophenyl)methyl]-2-oxoethyl}carbamoyl)(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylateHCID 69078909Tert-butyl 3-[n-((1r)-1-[(4-chlorophenyl)methyl]-2-oxo-2-{4-[2-(3-pyridylcarbonyl-amino)phenyl]piperazinyl}-ethyl)carbamoyl](3s)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

Product 1

HCID 10145823n-((1r)-1-[(4-Chlorophenyl)methyl]-2-oxo-2-{4-[2-(3-pyridylcarbonylamino)phenyl]piperazinyl}ethyl)((3s)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide

Procedure

Following the procedure for the synthesis of Preparation XIX, tert-butyl 3-[N-((1R)-1-[(4-chlorophenyl)methyl]-2-oxo-2-{4-[2-(3-pyridylcarbonyl-amino)phenyl]piperazinyl}-ethyl)carbamoyl](3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate was prepared from tert-butyl 3-(N-{(1R)-2-[4-(2-aminophenyl)piperazinyl]-1-[(4-chlorophenyl)methyl]-2-oxoethyl}carbamoyl)(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate (Preparation IX) (250 mg, 0.40 mmol), nicotinic acid (54 mg, 0.44 mmol) (Aldrich), 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide methiodide (227 mg; 0.76 mmol) and HOAT (62 mg; 0.46 mmol). The crude was concentrated in vacuo to afford of the desired compound (286 mg). MS (ESI, pos. ion) m/z: 723 (M+H), (ESI, neg. ion) m/z: 721 (M−H). Calc'd for C40H43ClN6O5: 723.26

Workup

  1. concentrationThe crude was concentrated in vacuo

Sources & evidence

ORD record
ord-6469e9ce663a4d72aff94f55ed4e4835
Source dataset
uspto-grants-2006_10
Patent number
US07115607B2

Reaction notes

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