Hydrazine hydrate (1:1) → HCID 58504576, compound

HRID 2367332Notes

Reaction equation

HRID 2367332 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][O:11][C@H:10]([CH2:15][NH:16][S:17]([CH3:20])(=[O:19])=[O:18])[CH2:9]2)[CH:5]=[C:4]([C:21]2[CH:26]=[CH:25][C:24]([C:27]#[N:28])=[C:23](F)[CH:22]=2)[N:3]=1.O.[NH2:31][NH2:32]>O1CCOCC1>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][O:11][C@H:10]([CH2:15][NH:16][S:17]([CH3:20])(=[O:19])=[O:18])[CH2:9]2)[CH:5]=[C:4]([C:21]2[CH:22]=[C:23]3[C:24]([C:27]([NH2:28])=[N:31][NH:32]3)=[CH:25][CH:26]=2)[N:3]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 58504524HCID 58504524, compound

Product 1

HCID 58504576HCID 58504576, compoundYield 26.8%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of crude N-({(2S,5R)-4-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-5-methyl-2-morpholinyl}methyl)methanesulfonamide (0.25 mmol theoretical) and hydrazine monohydrate (0.24 mL, 4.95 mmol) in 1,4-dioxane (3 mL) was stirred at 100° C. in a sealed tube for 17 hours. The mixture was concentrated in vacuo and the residue was purified on a Gilson reverse phase HPLC (CH3CN/water with 0.1% TFA). The product fractions were concentrated in vacuo, taken up in EtOAc (25 mL), washed with saturated aqueous NaHCO3 (2×15 mL) and brine (15 mL), then dried (Na2SO4), filtered, and concentrated in vacuo to afford the title compound (29 mg) as a pale yellow solid. LC-MS (ES) m/z=433 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.18 (d, J=6.6 Hz, 3H), 2.72-2.88 (m, 1H), 2.96 (s, 3H), 3.09-3.22 (m, 2H), 3.45-3.55 (m, 1H), 3.67 (dd, J=11.4, 2.5 Hz, 1H), 3.79 (d, J=11.1 Hz, 1H), 4.04-4.75 (bs, 2H), 5.39 (s, 2H), 6.14 (s, 2H), 6.56 (s, 1H), 7.23 (t, J=6.1 Hz, 1H), 7.57 (dd, J=8.6, 1.0 Hz, 1H), 7.72 (d, J=8.6 Hz, 1H), 7.94 (s, 1H), 11.53 (s, 1H).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customthe residue was purified on a Gilson reverse phase HPLC (CH3CN/water with 0.1% TFA)
  3. concentrationThe product fractions were concentrated in vacuo
  4. washwashed with saturated aqueous NaHCO3 (2×15 mL) and brine (15 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-31109187307b4d94876226aa3e25332d
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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