Hydrochloric Acid → Furo[3,2-c]pyridin-6-amine, 7-[1-(2,6-dichloro-3,5-difluorophenyl)ethoxy]-3-[1-(4-piperidinyl)-1H-pyrazol-4-yl]-

HRID 911979Notes

Reaction equation

[NH2:1][C:2]1[N:7]=[CH:6][C:5]2[C:8]([C:11]3[CH:12]=[N:13][N:14]([CH:16]4[CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][CH2:17]4)[CH:15]=3)=[CH:9][O:10][C:4]=2[C:3]=1[O:29][CH:30]([C:32]1[C:37]([Cl:38])=[C:36]([F:39])[CH:35]=[C:34]([F:40])[C:33]=1[Cl:41])[CH3:31].Cl>O1CCOCC1>[Cl:41][C:33]1[C:34]([F:40])=[CH:35][C:36]([F:39])=[C:37]([Cl:38])[C:32]=1[CH:30]([O:29][C:3]1[C:4]2[O:10][CH:9]=[C:8]([C:11]3[CH:12]=[N:13][N:14]([CH:16]4[CH2:17][CH2:18][NH:19][CH2:20][CH2:21]4)[CH:15]=3)[C:5]=2[CH:6]=[N:7][C:2]=1[NH2:1])[CH3:31]

Participants

Conditions

Temperature: 47.5 °C

Procedure

Into a round bottom flask were added tert-Butyl 4-(4-{6-amino-7-[1-(2,6-dichloro-3,5-difluorophenyl)ethoxy]furo[3,2-c]pyridin-3-yl}-1H-pyrazol-1-yl)piperidine-1-carboxylate (12.0 mg, 0.0197 mmol) and 1,4-Dioxane (3.0 mL, 38 mmol). 4 M HCl in 1,4-Dioxane (0.2 mL) was added slowly at 0° C. and the reaction mixture was stirred at rt (1 h), 30° C. (2 h), and 45-50° C. until completion. The reaction mixture was passed through SCX-2 and then purified by HPLC to afford the title compound. 1H NMR (400 MHz, CD3OD): δ=1.91 (d, J=6.8 Hz, 3H), 2.15-2.41 (m, 4H), 3.10-3.27 (m, 2H), 3.46-3.63 (m, 2H), 4.50-4.67 (m, 1H), 6.54 (q, J=6.7 Hz, 1H), 7.34 (t, J=8.7 Hz, 1H), 7.78 (s, 1H), 7.87 (s, 1H), 8.12 (s, 2H), 8.16 (s, 1H). MS (ES+): m/z 507.95/509.96 (40/24) [MH+]. HPLC: tR=2.56 min (ZQ3, polar—5 min).

Workup

custompurified by HPLC

Sources & evidence

ORD record: ord-3db584acdf384d16a55e84b174d11b24
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08022206B2

Reaction notes

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