Dimethylformamide → 4-{6-Amino-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-furo[3,2-c]pyridin-3-yl}-3,6-dihydro-2H-pyridine-1-carboxamide

HRID 911959노트

반응식

[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[C@H:10]([O:12][C:13]1[C:14]2[O:22][CH:21]=[C:20]([C:23]3[CH2:24][CH2:25][NH:26][CH2:27][CH:28]=3)[C:15]=2[CH:16]=[N:17][C:18]=1[NH2:19])[CH3:11].C[Si]([N:33]=[C:34]=[O:35])(C)C.CN(C=O)C.CCN(C(C)C)C(C)C>>[NH2:19][C:18]1[N:17]=[CH:16][C:15]2[C:20]([C:23]3[CH2:24][CH2:25][N:26]([C:34]([NH2:33])=[O:35])[CH2:27][CH:28]=3)=[CH:21][O:22][C:14]=2[C:13]=1[O:12][C@@H:10]([C:3]1[C:4]([Cl:9])=[CH:5][CH:6]=[C:7]([F:8])[C:2]=1[Cl:1])[CH3:11]

참가 물질

반응물 4

HCID 6228Dimethylformamide

HCID 70696Trimethylsilyl isocyanate

HCID 81531Diisopropylethylamine

HCID 578124807-[(R)-1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-3-(1,2,3,6-tetrahydropyridin-4-yl)furo[3,2-c]pyridin-6-ylamine

생성물 1

HCID 441816544-{6-Amino-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-furo[3,2-c]pyridin-3-yl}-3,6-dihydro-2H-pyridine-1-carboxamide

실험 절차

A mixture of 7-[(R)-1-(2,6-dichloro-3-fluorophenyl)-ethoxy]-3-(1,2,3,6-tetrahydropyridin-4-yl)-furo[3,2-c]pyridin-6-ylamine (9.00 mg, 0.0213 mmol), trimethylsilyl isocyanate (5.31 μL, 0.0392 mmol), DMF (0.5 mL, 0.005 mol), and DIPEA (0.03 mL, 0.2 mmol) was stirred at rt for 3 h. The solution was taken directly for HPLC purification. The fractions containing the pure product were concentrated in vacuo to afford the title compound as a yellow solid. 1H NMR (CD3OD, 400 MHz): δ=1.85-1.92 (m, 3H), 2.51 (br, s, 2H), 3.60-3.68 (m, 2H), 4.10 (br, s, 2H), 6.27 (d, J=3.5 Hz, 1H), 6.52 (q, J=6.8 Hz, 1H), 7.18-7.27 (m, 1H), 7.36-7.44 (m, 1H), 7.63-7.70 (m, 1H), 8.13-8.17 (m, 1H). MS (ES+): m/z 465.02 [MH+]. HPLC: tR=2.49 min (ZQ2, polar—5 min). The title compound was also converted to its mesylate and maleic acid salts by precipitation from ethanol.

후처리

customThe solution was taken directly for HPLC purification
additionThe fractions containing the pure product
concentrationwere concentrated in vacuo

출처 및 근거

ORD 기록: ord-6a25226dc0ea4fecbcd0eafcb5fa5775
출처 데이터셋: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
특허 번호: US08022206B2

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