Hydrazine hydrate (1:1) → HCID 46215127, compound

HRID 2367522Notes

Reaction equation

[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[C:13]([NH:15][CH3:16])[N:12]=[C:11]([N:17]3[C@H:22]([CH3:23])[CH2:21][O:20][C@H:19]([C:24]([NH:26][CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[O:25])[CH2:18]3)[CH:10]=2)=[CH:5][C:4]=1F)#[N:2].O.[NH2:36][NH2:37]>O1CCOCC1>[NH2:2][C:1]1[C:3]2[C:4](=[CH:5][C:6]([C:9]3[N:14]=[C:13]([NH:15][CH3:16])[N:12]=[C:11]([N:17]4[C@H:22]([CH3:23])[CH2:21][O:20][C@H:19]([C:24]([NH:26][CH2:27][C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=5)=[O:25])[CH2:18]4)[CH:10]=3)=[CH:7][CH:8]=2)[NH:37][N:36]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of (2S,5R)-4-[6-(4-cyano-3-fluorophenyl)-2-(methylamino)-4-pyrimidinyl]-5-methyl-N-(phenylmethyl)-2-morpholinecarboxamide (302 mg, 0.66 mmol) and hydrazine monohydrate (0.41 mL, 13.18 mmol) in 1,4-dioxane (5 mL) was stirred at 100° C. in a sealed tube for 18 hours. The reaction mixture was cooled and concentrated in vacuo, and the residue was purified by flash chromatography (60 g SiO2, CH2Cl2 to 90/10/1 CH2Cl2/CH3OH/NH4OH gradient) to give the title compound (239 mg) as a light yellow solid. LC-MS (ES) m/z=473 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.21 (d, J=6.6 Hz, 3H), 2.77-3.02 (m, 4H), 3.78 (d, J=11.2 Hz, 1H), 3.88 (d, J=11.1 Hz, 1H), 4.02 (dd, J=11.2, 2.9 Hz, 1H), 4.27-4.41 (m, 2H), 4.41-4.85 (bs, 2H), 5.39 (s, 2H), 6.51-6.72 (m, 2H), 7.19-7.38 (m, 5H), 7.62 (d, J=8.6 Hz, 1H), 7.72 (d, J=8.3 Hz, 1H), 7.99 (s, 1H), 8.54 (t, J=6.2 Hz, 1H), 11.50 (s, 1H).

Workup

temperatureThe reaction mixture was cooled
concentrationconcentrated in vacuo
customthe residue was purified by flash chromatography (60 g SiO2, CH2Cl2 to 90/10/1 CH2Cl2/CH3OH/NH4OH gradient)

Sources & evidence

ORD record: ord-5b2a29573ebe431f807dbbd3f9fac9ea
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08697685B2

Reaction notes

Loading…