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

HRID 228106Notes

Reaction equation

HRID 228106 reaction equation
CS(NC1C=CC=CC=1N1CCN(C(OC(C)(C)C)=O)CC1)(=O)=O.[NH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[N:32]1[CH2:37][CH2:36][N:35]([C:38](=[O:68])[C@H:39]([NH:48][C:49]([C@@H:51]2[CH2:60][C:59]3[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=3)[CH2:53][N:52]2[C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])=[O:50])[CH2:40][C:41]2[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][CH:42]=2)[CH2:34][CH2:33]1.N1C=CC=CC=1.[C:75]1([CH2:81][S:82](Cl)(=[O:84])=[O:83])[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=1>>[Cl:47][C:44]1[CH:43]=[CH:42][C:41]([CH2:40][C@@H:39]([NH:48][C:49]([C@@H:51]2[CH2:60][C:59]3[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=3)[CH2:53][N:52]2[C:61]([O:63][C:64]([CH3:65])([CH3:67])[CH3:66])=[O:62])=[O:50])[C:38](=[O:68])[N:35]2[CH2:36][CH2:37][N:32]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=3[NH:25][S:82]([CH2:81][C:75]3[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=3)(=[O:84])=[O:83])[CH2:33][CH2:34]2)=[CH:46][CH:45]=1.[Cl:47][C:44]1[CH:45]=[CH:46][C:41]([CH2:40][C@@H:39]([NH:48][C:49]([C@@H:51]2[CH2:60][C:59]3[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=3)[CH2:53][NH:52]2)=[O:50])[C:38](=[O:68])[N:35]2[CH2:34][CH2:33][N:32]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=3[NH:25][S:82]([CH2:81][C:75]3[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=3)(=[O:84])=[O:83])[CH2:37][CH2:36]2)=[CH:42][CH:43]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 74740Phenylmethanesulfonyl chlorideHCID 21935212Tert-Butyl 4-(2-[(Methylsulfonyl)Amino]Phenyl)-PiperazinecarboxylateHCID 58714321tert-butyl 3-(N-{(1R)-2-[4-(2-aminophenyl)piperazinyl]-1-[(4-chlorophenyl)methyl]-2-oxoethyl}carbamoyl)(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

Product 2

HCID 10146483n-{(1r)-1-[(4-Chlorophenyl)methyl]-2-oxo-2-[4-(2-{[benzylsulfonyl]amino}phenyl)piperazinyl]ethyl}((3s)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamideYield 95.9%HCID 69079094tert-Butyl 3-(N-{(1R)-1-[(4-chlorophenyl)methyl]-2-oxo-2-[4-(2-{[benzylsulfonyl]amino}phenyl)piperazinyl]ethyl}carbamoyl)(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

Procedure

tert-Butyl 3-(N-{(1R)-1-[(4-chlorophenyl)methyl]-2-oxo-2-[4-(2-{[benzylsulfonyl]amino}phenyl)piperazinyl]ethyl}carbamoyl)(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate was prepared according to the procedure for Preparation III using 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) (730 mg, 1.2 mmol), pyridine (100 μl, 1.2 mmol) and α-toluenesulfonyl chloride (240 mg, 1.2 mmol) (Aldrich). The crude material was purified by flash chromatography (SiO2 10% EtOAc in CH2Cl2) to afford the desired compound (387 mg). MS (ESI, pos. ion) m/z: 772 (M+H), (ESI, neg. ion) m/z: 770 (M−H). Calc'd for C41H46ClN5O6S: 772.35. Anal. Calcd for C41H46ClN5O6S-0.5 C4H8O2: C, 63.26; H, 6.17; N, 8.58; Cl, 4.34. Found C, 62.98; H, 6.09; N, 8.36.

Workup

  1. customThe crude material was purified by flash chromatography (SiO2 10% EtOAc in CH2Cl2)

Sources & evidence

ORD record
ord-d93661ebfa96409289bf57e8744a84f9
Source dataset
uspto-grants-2009_07
Patent number
US07560460B2

Reaction notes

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