Diisopropylethylamine → N2-(5-Cyclopropyl-1H-pyrazol-3-yl)-N6-[(1S)-1-(5-fluoropyridin-2-yl)ethyl]-3-nitropyridine-2,6-diamine

HRID 450361Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:13]=[C:12]([CH:14]3[CH2:16][CH2:15]3)[NH:11][N:10]=2)[C:5]([N+:17]([O-:19])=[O:18])=[CH:4][CH:3]=1.Cl.[F:21][C:22]1[CH:23]=[CH:24][C:25]([C@@H:28]([NH2:30])[CH3:29])=[N:26][CH:27]=1.C(N(C(C)C)CC)(C)C>CCCCO.C(OCC)(=O)C>[CH:14]1([C:12]2[NH:11][N:10]=[C:9]([NH:8][C:6]3[C:5]([N+:17]([O-:19])=[O:18])=[CH:4][CH:3]=[C:2]([NH:30][C@H:28]([C:25]4[CH:24]=[CH:23][C:22]([F:21])=[CH:27][N:26]=4)[CH3:29])[N:7]=3)[CH:13]=2)[CH2:16][CH2:15]1

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of 6-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)-3-nitropyridin-2-amine (Intermediate 9, 0.5 g) and [(1S)-1-(5-fluoropyridin-2-yl)ethyl]amine hydrochloride (Intermediate 5, 0.35 g) in n-BuOH (10 mL) with diisopropylethylamine (1 mL) was stirred at 70° C. for 4 hours. The resulting mixture was diluted with ethyl acetate (20 mL), and washed with brine (10 mL×3). The organic layer was dried and concentrated. The resulting residue was separated by silica gel column (Hexane/Ethyl acetate) to yield 0.45 g of desired product. MS (electrospray): 384 (M+1) for C18H18FN7O2. 1H NMR (300 MHz, CD3OD) δ ppm 8.60 (s, 1H) 8.20 (m, 1H) 8.15 (m, 1H) 7.60 (m, 1H) 7.40 (s, 1H) 6.30 (d, 1H) 6.20 (s, 1H) 5.35 (m, 1H), 1.90 (m, 1H) 1.60 (d, 3H) 1.00 (m, 2H) 0.80 (m, 2H).

Workup

washwashed with brine (10 mL×3)
customThe organic layer was dried
concentrationconcentrated
customThe resulting residue was separated by silica gel column (Hexane/Ethyl acetate)

Sources & evidence

ORD record: ord-f021bfc774554b07ac4ccd07c80f66f6
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08486966B2

Reaction notes

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