Diisopropylethylamine → N-(3,3-difluorocyclobutyl)-2-(4-(2,4-difluorophenoxyl)piperidin-1-yl)pyrido[3,4-b]pyrazin-3-amine

HRID 713208Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]2[CH:8]=[N:9][CH:10]=[CH:11][C:5]2=[N:4][C:3]=1[N:12]1[CH2:17][CH2:16][CH:15]([O:18][C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])[CH2:14][CH2:13]1.Cl.[F:28][C:29]1([F:34])[CH2:32][CH:31]([NH2:33])[CH2:30]1.[F-].[K+].CCN(C(C)C)C(C)C>CS(C)=O.O>[F:28][C:29]1([F:34])[CH2:32][CH:31]([NH:33][C:2]2[N:7]=[C:6]3[CH:8]=[N:9][CH:10]=[CH:11][C:5]3=[N:4][C:3]=2[N:12]2[CH2:17][CH2:16][CH:15]([O:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])[CH2:14][CH2:13]2)[CH2:30]1

Participants

Conditions

Temperature: 23 °C

Procedure

Combined 3-chloro-2-(4-(2,4-difluorophenoxyl)piperidin-1-yl)pyrido[3,4-b]pyrazine (0.46 g, 1.221 mmol), 3,3-difluorocyclobutanamine hydrochloride (0.526 g, 3.66 mmol), and potassium fluoride (0.092 g, 1.587 mmol) in DMSO (5 mL) and added DIPEA (1.063 mL, 6.10 mmol) at 23° C. The reaction was stirred at 23° C. for 5 days and diluted with water (20 mL) to furnish a yellow-orange suspension. The resulting solid was filtered, rinsed with water, and dried in vacuo to give the title compound (516.4 mg, 95%) as a yellow-orange solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 1.87-1.98 (m, 2H), 2.07-2.18 (m, 2H), 2.77-2.91 (m, 2H), 2.96-3.07 (m, 2H), 3.23-3.32 (m, 2H), 3.69-3.78 (m, 2H), 4.35-4.45 (m, 1H), 4.63 (tt, J=7.9, 3.8 Hz, 1H), 7.00-7.07 (m, 1H), 7.24-7.40 (m, 3H), 7.48 (d, J=5.4 Hz, 1H), 8.33 (d, J=5.4 Hz, 1H), 8.82 (s, 1H); ESI-MS m/z [M+H]+ 447.9.

Workup

customto furnish a yellow-orange suspension
filtrationThe resulting solid was filtered
washrinsed with water
customdried in vacuo

Sources & evidence

ORD record: ord-5b3bc6a84bdb4e1c9d138b05abff9b71
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181249B2

Reaction notes

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