Hydrazine hydrate (1:1) → HCID 46215128, compound

HRID 2367519Notes

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][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[O:25])[CH2:18]3)[CH:10]=2)=[CH:5][C:4]=1F)#[N:2].O.[NH2:35][NH2:36]>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][C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=5)=[O:25])[CH2:18]4)[CH:10]=3)=[CH:7][CH:8]=2)[NH:36][N:35]=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-phenyl-2-morpholinecarboxamide (340 mg, 0.61 mmol) and hydrazine monohydrate (0.39 mL, 12.54 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 (243 mg) as a pale yellow solid. LC-MS (ES) m/z=459 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.24 (d, J=6.6 Hz, 3H), 2.86 (d, J=4.0 Hz, 3H), 2.97-3.15 (m, 1H), 3.83 (d, J=11.1 Hz, 1H), 3.94 (d, J=11.1 Hz, 1H), 4.16 (dd, J=11.2, 2.9 Hz, 1H), 4.33-4.88 (bs, 2H), 5.39 (s, 2H), 6.56-6.73 (m, 2H), 7.10 (t, J=7.3 Hz, 1H), 7.34 (t, J=7.9 Hz, 2H), 7.63 (d, J=8.3 Hz, 1H), 7.73 (d, J=8.3 Hz, 3H), 8.01 (s, 1H), 9.88 (s, 1H), 11.51 (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-846b95388cdd42a997e2a660bb573a5c
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08697685B2

Reaction notes

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