Tetrahydrofuran → 5,6-difluoro-N-(4-(3-(2-(methylthio)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-1H-benzo[d]imidazol-2-amine

HRID 252648

Reaction equation

[N:1]([C:4]1[CH:24]=[CH:23][C:7]([O:8][C:9]2[C:14]([C:15]3[CH:20]=[CH:19][N:18]=[C:17]([S:21][CH3:22])[N:16]=3)=[CH:13][CH:12]=[CH:11][N:10]=2)=[CH:6][CH:5]=1)=[C:2]=S.C1CCC(N=C=NC2CCCCC2)CC1.[F:40][C:41]1[CH:42]=[C:43]([NH2:49])[C:44]([NH2:48])=[CH:45][C:46]=1[F:47].C1COCC1>C(Cl)Cl>[F:40][C:41]1[C:46]([F:47])=[CH:45][C:44]2[NH:48][C:2]([NH:1][C:4]3[CH:24]=[CH:23][C:7]([O:8][C:9]4[C:14]([C:15]5[CH:20]=[CH:19][N:18]=[C:17]([S:21][CH3:22])[N:16]=5)=[CH:13][CH:12]=[CH:11][N:10]=4)=[CH:6][CH:5]=3)=[N:49][C:43]=2[CH:42]=1

Participants

Conditions

Temperature: 70 °C

Procedure

A resealable pressure vial, under nitrogen, was charged with 4-(2-(4-isothiocyanatophenoxy)pyridin-3-yl)-2-(methylthio)pyrimidine (1.12 g, 3.18 mmol), PS-DCC (1.27 mmol/g polymer supported cyclohexyl carbodiimide) (7.50 g, 9.53 mmol), 4,5-difluorobenzene-1,2-diamine (0.69 g, 4.77 mmol), and THF (45 ml, 0.07 M). The vessel was sealed and the reaction mixture stirred at 70° C. for 4 h. The reaction mixture was cooled to RT, diluted with DCM, and filtered over celite. The filtrate was concentrated to afford yellow residue, which was triturated with DCM, filtered, and dried under high vacuum to afford 5,6-difluoro-N-(4-(3-(2-(methylthio)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-1H-benzo[d]imidazol-2-amine as a tan solid. MS m/z=463.1 [M+H]+. Calc'd for C23H16F2N6OS: 462.48.

Workup

customThe vessel was sealed
temperatureThe reaction mixture was cooled to RT
filtrationfiltered over celite
concentrationThe filtrate was concentrated
customto afford yellow residue, which
customwas triturated with DCM
filtrationfiltered
customdried under high vacuum

Sources & evidence

ORD record: ord-e1f3622889764387952ef6c3d4aee72f
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07868177B2

Linked notes

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