Methanesulfonyl chloride → Fluoren-9-ylmethyl (3R)-3-{N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]carbamoyl}-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

HRID 228080Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:54])[C@H:15]([NH:24][C:25]([C@H:27]2[CH2:36][C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH2:29][N:28]2[C:37]([O:39][CH2:40][CH:41]2[C:53]3[CH:52]=[CH:51][CH:50]=[CH:49][C:48]=3[C:47]3[C:42]2=[CH:43][CH:44]=[CH:45][CH:46]=3)=[O:38])=[O:26])[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[CH2:10][CH2:9]1.[CH3:55][S:56](Cl)(=[O:58])=[O:57].C(C1C=CC=C(C(C)(C)C)N=1)(C)(C)C>>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([CH2:16][C@@H:15]([NH:24][C:25]([C@H:27]2[CH2:36][C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH2:29][N:28]2[C:37]([O:39][CH2:40][CH:41]2[C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][C:47]=3[C:48]3[C:53]2=[CH:52][CH:51]=[CH:50][CH:49]=3)=[O:38])=[O:26])[C:14]([N:11]2[CH2:10][CH2:9][N:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[NH:1][S:56]([CH3:55])(=[O:58])=[O:57])[CH2:13][CH2:12]2)=[O:54])=[CH:18][CH:19]=1

Participants

Reactant 3

HCID 31297Methanesulfonyl chloride

HCID 685102,6-Di-tert-butylpyridine

HCID 58714327Fluoren-9-ylmethyl (3R)-3-(N-{(1R)-2-[4-(2-aminophenyl)piperazinyl]-1-[(4-chlorophenyl)methyl]-2-oxoethyl}carbamoyl)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

Product 1

HCID 58714322Fluoren-9-ylmethyl (3R)-3-{N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]carbamoyl}-1,2,3,4-tetrahydroisoquinoline-2-carboxylateYield 86.3%

Procedure

Fluoren-9-ylmethyl (3R)-3-{N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]carbamoyl}-1,2,3,4-tetrahydroisoquinoline-2-carboxylate was prepared from fluoren-9-ylmethyl (3R)-3-(N-{(1R)-2-[4-(2-aminophenyl)piperazinyl]-1-[(4-chlorophenyl)methyl]-2-oxoethyl}carbamoyl)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate (250 mg, 0.34 mmol) according to the procedure for Preparation III using methanesulfonyl chloride (30 μl, 0.39 mmol) and 2,6-di-tert-butyl-pyridine (80 μl, 0.36 mmol) (Aldrich). The crude product was concentrated in vacuo and purified by flash chromatography (SiO2, 15% EtOAc in CH2Cl2), to afford the desired compound (240 mg). MS (ESI, pos. ion) m/z: 818 (M+H), (ESI, neg. ion) m/z: 816 (M−H). Calc'd for C45H44ClN5O6S: 817.27.

Workup

concentrationThe crude product was concentrated in vacuo
custompurified by flash chromatography (SiO2, 15% EtOAc in CH2Cl2)

Sources & evidence

ORD record: ord-a964f2176dd44c3abf7740851995f468
Source dataset: uspto-grants-2009_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07560460B2

Reaction notes

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