Hydrazine hydrate (1:1) → HCID 58504735, compound

HRID 2367526Notes

Reaction equation

[CH3:1][N:2]([CH2:4][C@H:5]1O[CH2:9][C@@H:8]([CH3:11])[N:7]([C:12]2[N:17]=[C:16]([NH:18][CH3:19])[N:15]=[C:14]([C:20]3[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[C:22](F)[CH:21]=3)[CH:13]=2)[CH2:6]1)[CH3:3].[OH2:29].[NH2:30][NH2:31]>O1CCOCC1>[CH3:1][N:2]([CH2:4][C@H:5]1[O:29][CH2:11][C@@H:8]([CH3:9])[N:7]([C:12]2[N:17]=[C:16]([NH:18][CH3:19])[N:15]=[C:14]([C:20]3[CH:27]=[C:26]4[C:23]([C:24]([NH2:25])=[N:30][NH:31]4)=[CH:22][CH:21]=3)[CH:13]=2)[CH2:6]1)[CH3:3]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 4-[6-{(2R,5R)-2-[(dimethylamino)methyl]-5-methyl-4-morpholinyl}-2-(methylamino)-4-pyrimidinyl]-2-fluorobenzonitrile (58 mg, 0.15 mmol) and hydrazine monohydrate (0.10 mL, 3.21 mmol) in 1,4-dioxane (2 mL) was stirred at 100° C. in a sealed tube for 15 hours. The reaction mixture was then cooled and concentrated in vacuo, and the residue was purified by flash chromatography (24 g SiO2, CH2Cl2 to 90/10/1 CH2Cl2/CH3OH/NH4OH gradient) to give the title compound (44 mg) as an off-white solid. LC-MS (ES) m/z=397 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.17 (d, J=6.6 Hz, 3H), 2.22 (s, 6H), 2.35-2.45 (m, 2H), 2.66-2.80 (m, 1H), 2.84 (d, J=4.3 Hz, 3H), 3.49-3.60 (m, 1H), 3.66 (d, J=11.4 Hz, 1H), 3.75 (d, J=11.1 Hz, 1H), 4.02-4.79 (bs, 2H), 5.38 (s, 2H), 6.48-6.65 (m, 2H), 7.60 (d, J=8.6 Hz, 1H), 7.72 (d, J=8.3 Hz, 1H), 7.98 (s, 1H), 11.50 (s, 1H).

Workup

temperatureThe reaction mixture was then cooled
concentrationconcentrated in vacuo
customthe residue was purified by flash chromatography (24 g SiO2, CH2Cl2 to 90/10/1 CH2Cl2/CH3OH/NH4OH gradient)

Sources & evidence

ORD record: ord-9e0e6cea2a2c40afadcf44bc630a1fc9
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08697685B2

Reaction notes

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