1,2-Dichloroethane → HCID 90094657, compound

HRID 927285Notes

Reaction equation

HRID 927285 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C@H:8]([NH:12][C:13]([C:15]1[CH:16]=[C:17]3[C:22](=[CH:23][CH:24]=1)[C:21](=[O:25])[N:20]([C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=1)[C:19]([CH2:33][CH2:34][CH2:35][CH2:36][C:37](O)=[O:38])=[CH:18]3)=[O:14])[CH2:7][CH2:6][CH2:5]2.[CH:40]1([S:43]([NH2:46])(=[O:45])=[O:44])[CH2:42][CH2:41]1.C(Cl)CCl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH:40]1([S:43]([NH:46][C:37](=[O:38])[CH2:36][CH2:35][CH2:34][CH2:33][C:19]2[N:20]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)[C:21](=[O:25])[C:22]3[C:17]([CH:18]=2)=[CH:16][C:15]([C:13]([NH:12][C@H:8]2[C:9]4[C:4](=[CH:3][C:2]([F:1])=[CH:11][CH:10]=4)[CH2:5][CH2:6][CH2:7]2)=[O:14])=[CH:24][CH:23]=3)(=[O:45])=[O:44])[CH2:42][CH2:41]1

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 15765418CyclopropanesulfonamideHCID 90096261HCID 90096261, compound

Product 1

HCID 90094657HCID 90094657, compoundYield 64.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of (R)-5-(6-((6-fluoro-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoic acid (10 mg, 0.019 mmol), cyclopropanesulfonamide (3.43 mg, 0.028 mmol, 1.50 equiv.), DMAP (4.61 mg, 0.038 mmol, 2.0 equiv.) and EDC (7.23 mg, 0.038 mmol, 2.0 equiv.) in DCM (1 mL) was stirred at room temperature overnight. The residue was purified by column chromatography on silica gel eluting with 0-3% CH2Cl2/MeOH to give 7.8 mg of (R)-3-(5-(cyclopropanesulfonamido)-5-oxopentyl)-N-(6-fluoro-1,2,3,4-tetrahydronaphthalen-1-yl)-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-6-carboxamide as a white solid. LCMS [M+H]+=634. 1H NMR (DMSO, 500 MHz) δ ppm: 8.18 (dd, J=8.0, 3.5 Hz, 2H), 7.91 (d, J=8.0 Hz, 1H), 7.43-7.36 (m, 4H), 7.26 (t, J=7.0 Hz, 1H), 7.00 (t, J=8.5 Hz, 2H), 6.66 (s, 1H), 5.26-5.22 (m, 1H), 2.85-2.74 (m, 3H), 2.30-2.15 (m, 4H), 2.09 (t, J=7.0 Hz, 2H), 2.00-1.96 (m, 2H), 1.91-1.76 (m, 2H), 1.45-1.39 (m, 4H), 1.10-1.00 (m, 4H).

Workup

  1. customThe residue was purified by column chromatography on silica gel eluting with 0-3% CH2Cl2/MeOH

Sources & evidence

ORD record
ord-b397a68a46cf44bfbe22ec8f5129d8e7
Source dataset
uspto-grants-2016_03
Patent number
US09290454B2

Reaction notes

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