Triethylamine → N-[9-(dichloromethylene)-1,2,3,4-tetrahydro-1,4-methanonaphthalen-5-yl]-3-(difluoromethyl)-1-methylpyrazole-4-carboxamide

HRID 1897744Notes

Reaction equation

[Cl:1][C:2]([Cl:15])=[C:3]1[CH:7]2[C:8]3[C:13]([CH:4]1[CH2:5][CH2:6]2)=[CH:12][CH:11]=[CH:10][C:9]=3[NH2:14].C(N(CC)CC)C.[F:23][CH:24]([F:34])[C:25]1[C:29]([C:30](Cl)=[O:31])=[CH:28][N:27]([CH3:33])[N:26]=1>C1(C)C(C)=CC=CC=1>[Cl:1][C:2]([Cl:15])=[C:3]1[CH:7]2[C:8]3[C:13]([CH:4]1[CH2:5][CH2:6]2)=[CH:12][CH:11]=[CH:10][C:9]=3[NH:14][C:30]([C:29]1[C:25]([CH:24]([F:34])[F:23])=[N:26][N:27]([CH3:33])[CH:28]=1)=[O:31]

Participants

Conditions

Temperature: 80 °C

Procedure

9-Dichloromethylene-1,2,3,4-tetrahydro-1,4-methano-naphthalen-5-ylamine (166 g, 35% xylene solution, 0.25 mol), triethylamine (28 g, 0.275 mol) and xylene (13 g) were charged in a reactor and the mixture was heated to 80° C. 3-Difluoromethyl-1-methyl-1H-pyrazole-4-carbonyl chloride (182 g, 26% xylene solution, 0.25 mol) was added over 2 hours. After conversion, the product was extracted, concentrated and crystallized in a mixture of xylene/methycyclohexane. 83 g of pure product were isolated. (Purity: 97%, Yield: 82%) 1H-NMR (400 MHz, CDCl3): δ=8.12 (bs, 1H, NH); 8.05 (s, 1H, Pyr-H); 7.83-7.80 (d, 1H, Ar—H); 7.19-7.15 (t, 1H, Ar—H); 7.04 (d, 1H, Ar—H); 7.02-6.76 (t, 1H, CHF2); 4.1 (s, 1H, CH); 3.95-4.0 (bs, 4H, CH & CH3); 2.18-2.08 (m, 2H, CH2); 1.55-1.3 (2m, 2H, CH2).

Workup

extractionAfter conversion, the product was extracted
concentrationconcentrated
customcrystallized in a mixture of xylene/methycyclohexane

Sources & evidence

ORD record: ord-16a94346ef7043549b00db3e271af706
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08519151B2

Reaction notes

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