L-Tartaric acid → HCID 131732859, compound

HRID 576117Notes

Reaction equation

HRID 576117 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[C:18]3[C:13](=[CH:14][C:15]([C:20]4[CH:28]=[CH:27][C:23]([C:24]([NH2:26])=[O:25])=[CH:22][CH:21]=4)=[C:16]([F:19])[CH:17]=3)[CH2:12][NH:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].[C:29]([OH:38])(=[O:37])[C@@H:30]([C@H:32]([C:34]([OH:36])=[O:35])[OH:33])[OH:31]>C(#N)C.O>[C:34]([C@@H:32]([C@H:30]([C:29]([OH:38])=[O:37])[OH:31])[OH:33])([OH:36])=[O:35].[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[C:18]3[C:13](=[CH:14][C:15]([C:20]4[CH:28]=[CH:27][C:23]([C:24]([NH2:26])=[O:25])=[CH:22][CH:21]=4)=[C:16]([F:19])[CH:17]=3)[CH2:12][NH:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

5

Reactant 2

HCID 444305L-Tartaric acidHCID 49805026HCID 49805026, compound

Product 1

HCID 131732859HCID 131732859, compoundYield 102.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To an ice-cold solution of bis-Boc protected 4-(4-(3,4-dichlorophenyl)-6-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)benzamide (515 mg, 0.82 mmol) and N1,N1,N8,N8-tetramethylnaphthalene-1,8-diamine (527 mg, 2.46 mmol) in 1,2-dichloroethane (15 mL) was added 1-chlorethyl chloroformate (0.27 mL, 2.46 mmol) drop wise. The mixture was stirred for 15 minutes and then heated to 40° C. for 2 hours. The mixture was concentrated and filtered through a pad of silica gel (1:1:1 hexanes/ethyl acetate/dichloromethane). The filtrate was concentrated, the residue dissolved in methanol (5 mL) and heated to reflux for 1 hour and then concentrated. The residue was dissolved in dichloromethane (5 mL) and trifluoroacetic acid (5 mL), stirred for 2 hours, concentrated and purified by semi-preparative HPLC, and neutralized with saturated sodium bicarbonate and ethyl acetate to give 4-(4-(3,4-dichlorophenyl)-6-fluoro-1,2,3,4-tetrahydroisoquinolin-7-yl)benzamide as an off-white solid (95 mg, 28%). A mixture of 4-(4-(3,4-dichlorophenyl)-6-fluoro-1,2,3,4-tetrahydroisoquinolin-7-yl)benzamide (20 mg, 0.05 mmol) and L-tartaric acid (7 mg, 0.05 mmol) in acetonitrile and water was lyophilized to give 4-(4-(3,4-dichlorophenyl)-6-fluoro-1,2,3,4-tetrahydroisoquinolin-7-yl)benzamide, L-tartrate salt (29 mg, 100%): 1H NMR (CD3OD, 500 MHz) δ 7.96 (dd, J=6.5, 2.0 Hz, 2H), 7.67-7.65 (m, 2H), 7.57 (d, J=8.0 Hz, 1H), 7.51 (d, J=2.0 Hz, 1H), 7.49 (d, J=7.5 Hz, 1H), 7.24 (dd, J=8.5, 2.5 Hz, 1H), 6.73 (d, J=11.5 Hz, 1H), 4.58-4.44 (m, 3H), 4.43 (s, 2.6H), 3.80-3.75 (m, 1H), 3.45-3.40 (m, 1H); ESI MS m/z 415 [M+H]+.

Sources & evidence

ORD record
ord-63487d2904a549d8a86b4a18fd6dde21
Source dataset
uspto-grants-2015_05
Patent number
US09034899B2

Reaction notes

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