Hydrazine hydrate (1:1) → HCID 58504777, compound

HRID 2367330Notes

Reaction equation

HRID 2367330 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][C:17](=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:9]2)[CH:5]=[C:4]([C:23]2[CH:28]=[CH:27][C:26]([C:29]#[N:30])=[C:25](F)[CH:24]=2)[N:3]=1.O.[NH2:33][NH2:34]>C(O)C>[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][C:17](=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:9]2)[CH:5]=[C:4]([C:23]2[CH:24]=[C:25]3[C:26]([C:29]([NH2:30])=[N:33][NH:34]3)=[CH:27][CH:28]=2)[N:3]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 58504662HCID 58504662, compound

Product 1

HCID 58504777HCID 58504777, compoundYield 63.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of crude N-({(2R,5R)-4-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-5-methyl-2-morpholinyl}methyl)-2,2-dimethylpropanamide (0.29 mmol theoretical) and hydrazine monohydrate (0.28 mL, 5.78 mmol) in ethanol (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 combined and concentrated in vacuo, taken up in EtOAc (15 mL), washed with saturated aqueous NaHCO3 (2×10 mL) and brine (10 mL), then dried (Na2SO4), filtered, and concentrated in vacuo to afford the title compound (81 mg) as a pale yellow solid. LC-MS (ES) m/z=439 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.13 (s, 9H), 1.17 (d, J=6.6 Hz, 3H), 2.64-2.84 (m, 1H), 3.20-3.30 (m, 2H), 3.42-3.52 (m, 1H), 3.63 (dd, J=11.4, 2.5 Hz, 1H), 3.77 (d, J=11.1 Hz, 1H), 3.98-4.79 (bs, 2H), 5.39 (s, 2H), 6.12 (s, 2H), 6.50 (s, 1H), 7.53 (d, J=8.3 Hz, 1H), 7.63 (t, J=5.7 Hz, 1H), 7.71 (d, J=8.3 Hz, 1H), 7.93 (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. concentrationconcentrated in vacuo
  4. washwashed with saturated aqueous NaHCO3 (2×10 mL) and brine (10 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1fb2d4ca4e584d9db5e2efc0d8178983
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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