Hydrazine hydrate (1:1) → 6-(3-Amino-1H-indazol-6-yl)-N4-[1-(phenylmethyl)cyclopropyl]-2,4-pyrimidinediamine

HRID 2367258Notes

Reaction equation

[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10](F)[CH:9]=2)[CH:5]=[C:4]([NH:17][C:18]2([CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:20][CH2:19]2)[N:3]=1.O.[NH2:29][NH2:30]>C(O)C>[NH2:13][C:12]1[C:11]2[C:10](=[CH:9][C:8]([C:6]3[N:7]=[C:2]([NH2:1])[N:3]=[C:4]([NH:17][C:18]4([CH2:21][C:22]5[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=5)[CH2:20][CH2:19]4)[CH:5]=3)=[CH:15][CH:14]=2)[NH:30][N:29]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 4-(2-amino-6-{[1-(phenylmethyl)cyclopropyl]amino}-4-pyrimidinyl)-2-fluorobenzonitrile (124 mg, 0.34 mmol) and hydrazine hydrate (99%, 2 mL) in ethanol (10 mL) was stirred and heated at 120° C. for 1 hour in a Biotage Initiator microwave synthesizer. The mixture was cooled to room temperature, filtered and concentrated in vacuo. The resulting solids were purified by reverse phase chromatography with CH3CN in water (0.08% ammonium hydrogen carbonate) (gradient: 35% to 45% in 6 min: flowrate: 30 mL/min), to afford the title compound (30 mg) as a white solid. LC-MS (ES) m/z=372 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.78 (d, 4H), 2.93 (s, 2H), 5.37 (s, 2H), 5.97 (s, 2H), 6.32 (s, 1H), 6.90 (s, 1H), 7.18 (d, 3H), 7.27 (t, 2H), 7.40 (s, 1H), 7.69 (d, 1H), 7.81 (s, 1H), 11.50 (s, 1H).

Workup

temperatureThe mixture was cooled to room temperature
filtrationfiltered
concentrationconcentrated in vacuo
customThe resulting solids were purified by reverse phase chromatography with CH3CN in water (0.08% ammonium hydrogen carbonate) (gradient: 35% to 45% in 6 min: flowrate: 30 mL/min)

Sources & evidence

ORD record: ord-0f0fb185f7504708be636afc3476d64c
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08697685B2

Reaction notes

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