1,2-Dichloroethane → n-[(1r)-1-[(3,4-Dichlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]((3s)(3-1,2,3,4-tetrahydroisoquinolyl))-carboxamide

HRID 228082Notes

Reaction equation

HRID 228082 reaction equation
Cl.[CH3:2][S:3]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)(=[O:5])=[O:4].[CH3:19][C:20]([O:23][C:24]([NH:26][C@@H:27]([C:37]([OH:39])=[O:38])[CH2:28][C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[C:31]([Cl:36])[CH:30]=1)=[O:25])([CH3:22])[CH3:21].CC[N:42]([CH:46]([CH3:48])C)[CH:43]([CH3:45])C.C(Cl)CCl.[CH:53]1[CH:58]=N[C:56]2N(O)N=N[C:55]=2[CH:54]=1>CN(C=O)C>[Cl:36][C:31]1[CH:30]=[C:29]([CH2:28][C@@H:27]([NH:26][C:24]([O:23][C:20]([CH3:22])([CH3:21])[CH3:19])=[O:25])[C:37]([N:16]2[CH2:17][CH2:18][N:13]([C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=3[NH:6][S:3]([CH3:2])(=[O:4])=[O:5])[CH2:14][CH2:15]2)=[O:38])[CH:34]=[CH:33][C:32]=1[Cl:35].[Cl:36][C:31]1[CH:30]=[C:29]([CH2:28][C@@H:27]([NH:26][C:24]([C@@H:46]2[CH2:48][C:56]3[C:45](=[CH:58][CH:53]=[CH:54][CH:55]=3)[CH2:43][NH:42]2)=[O:25])[C:37]([N:16]2[CH2:17][CH2:18][N:13]([C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=3[NH:6][S:3]([CH3:2])(=[O:4])=[O:5])[CH2:14][CH2:15]2)=[O:39])[CH:34]=[CH:33][C:32]=1[Cl:35]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 70158113,4-Dichloro-N-((1,1-dimethylethoxy)carbonyl)-D-phenylalanineHCID 21283546N-(2-(Piperazin-1-yl)phenyl)methanesulfonamide hydrochloride

Product 2

HCID 10282776n-[(1r)-1-[(3,4-Dichlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]((3s)(3-1,2,3,4-tetrahydroisoquinolyl))-carboxamideYield 113.3%HCID 21060073n-[(1r)-1-[(3,4-Dichlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl](tert-butoxy)carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-[(1R)-1-[(3,4-Dichlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl](tert-butoxy)carboxamide was prepared according to the procedure for Preparation XIX using (methylsulfonyl)(2-piperazinylphenyl)amine hydrochloride (800 mg, 2.8 mmol), N-Boc-D-3,4-dichlorophenylalanine (930 mg, 2.80 mmol) (Peptech), DIEA (480 μl, 2.80 mmol), EDC (1.66 g, 5.60 mmol), HOAT (400 mg, 3.0 mmol) and DMF (10 mL). The crude product was purified by flash chromatography (SiO2, 1:1 hexane:EtOAc) and concentrated in vacuo to afford the desired compound (1.0 g). MS (ESI, pos. ion) m/z: 571 (M+H), (ESI, neg. ion) m/z: 569 (M−H). Calc'd for C25H32Cl2N4O5S: 570.15.

Workup

  1. customThe crude product was purified by flash chromatography (SiO2, 1:1 hexane:EtOAc)
  2. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-965145ba56bd43d9bbff5519d303565f
Source dataset
uspto-grants-2009_07
Patent number
US07560460B2

Reaction notes

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