Hydrazine → (3S)-1-[2-Amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-N-(2-fluorophenyl)-3-piperidinecarboxamide

HRID 2367456Notes

Reaction equation

[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][C@H:10]([C:14]([NH:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[F:23])=[O:15])[CH2:9]2)[CH:5]=[C:4]([C:24]2[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[C:26](F)[CH:25]=2)[N:3]=1.CCN(C(C)C)C(C)C.[NH2:42][NH2:43]>CCO>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][C@H:10]([C:14]([NH:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[F:23])=[O:15])[CH2:9]2)[CH:5]=[C:4]([C:24]2[CH:25]=[C:26]3[C:27]([C:30]([NH2:31])=[N:42][NH:43]3)=[CH:28][CH:29]=2)[N:3]=1

Participants

Conditions

Temperature: 150 °C

Procedure

Into a microwave tube, (3S)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-N-(2-fluorophenyl)-3-piperidinecarboxamide (191 mg, 0.440 mmol), 3 mL of EtOH, Hunig's base (0.077 mL, 0.440 mmol), and hydrazine anhydrous (0.055 mL, 1.759 mmol) were added, and the resulting yellow mixture was heated at 150° C. for 150 minutes under microwave conditions. The solution turned black. LCMS showed mainly product. The black solids were filtered and the yellow filtrate was evaporated. The yellow residue was dissolved in CH3OH, and purified by HPLC (CH3CN/H2O w/0.1% HCO2H) to afford a formic acid salt of the title compound (20 mg) as a light yellow solid. LC-MS (ES) m/z=447 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.51 (m, 1H), 1.84 (m, 2H), 2.01-2.20 (m, 1H), 3.21-3.24 (m, 2H), 3.44-3.61 (m, 1H), 4.36-4.53 (m, 1H), 4.61-5.09 (m, 1H), 6.97 (m, 1H), 7.17 (m, 3H), 7.39 (s, 1H), 7.67-8.01 (m, 3H), 9.84 (m, 1H), 11.87-12.17 (m, 2H).

Workup

filtrationThe black solids were filtered
customthe yellow filtrate was evaporated
dissolutionThe yellow residue was dissolved in CH3OH
custompurified by HPLC (CH3CN/H2O w/0.1% HCO2H)

Sources & evidence

ORD record: ord-6f8d97348d8943dbb262643c0c7c25b1
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08697685B2

Reaction notes

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