Diisopropylethylamine → 5-Nitro-N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]pyrimidine-2,4-diamine

HRID 415409Notes

Reaction equation

Cl.[F:2][C:3]1[CH:4]=[N:5][C:6]([C@@H:9]([NH2:11])[CH3:10])=[N:7][CH:8]=1.Cl[C:13]1[N:18]=[C:17]([NH:19][C:20]2[CH:24]=[C:23]([CH:25]3[CH2:27][CH2:26]3)[NH:22][N:21]=2)[C:16]([N+:28]([O-:30])=[O:29])=[CH:15][N:14]=1.CCN(C(C)C)C(C)C>CCCCO>[N+:28]([C:16]1[C:17]([NH:19][C:20]2[CH:24]=[C:23]([CH:25]3[CH2:27][CH2:26]3)[NH:22][N:21]=2)=[N:18][C:13]([NH:11][C@H:9]([C:6]2[N:7]=[CH:8][C:3]([F:2])=[CH:4][N:5]=2)[CH3:10])=[N:14][CH:15]=1)([O-:30])=[O:29]

Participants

Conditions

Temperature: 60 °C

Procedure

A 20 mL round bottom flask was charged with (S)-1-(5-Fluoropyrimidin-2-yl)ethanamine hydrochloride (Method 7, 0.25 g, 1.77 mmol), 2-Chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)-5-nitropyrimidin-4-amine (Method 37, 0.3 g, 1.0 mmol), and DIEA (0.30 g, 2.34 mmol). Anhydrous n-BuOH (5 mL) was added, and the flask was heated at 60° C. for 4 hours. The reaction mixture was washed with brine (5 mL×3), and the organic layer was dried and concentrated. The resulting residue was separated by silica gel column to afford desired product (0.3 g, 75%). LC-MS, 386 (M+1). 1H NMR (DMSO-d6) δ 12.3 (s, 1H), 10.5 (s, 1H), 9.1 (s, 1H), 9.0 (s, 1H), 8.80 (s, 2H), 6.1 (s, 1H), 5.2 (dd, 1H), 2.0 (m, 1H), 1.7 (d, 3H), 1.0 (m, 2H), 0.8 (m, 2H).

Workup

washThe reaction mixture was washed with brine (5 mL×3)
customthe organic layer was dried
concentrationconcentrated
customThe resulting residue was separated by silica gel column

Sources & evidence

ORD record: ord-0c6644de22934c9282ec4af1db42c3e3
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08088784B2

Reaction notes

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