Hydrazine hydrate (1:1) → HCID 58504834, compound

HRID 2367614Notes

Reaction equation

HRID 2367614 reaction equation
F[C:2]1[CH:9]=[C:8]([C:10]2[CH:15]=[C:14]([N:16]3[CH2:20][CH2:19][CH2:18][C@H:17]3[C:21]([F:24])([F:23])[F:22])[N:13]=[C:12]([NH:25][CH3:26])[N:11]=2)[CH:7]=[C:6]([O:27][CH3:28])[C:3]=1[C:4]#[N:5].O.[NH2:30][NH2:31]>C(O)C>[CH3:26][NH:25][C:12]1[N:11]=[C:10]([C:8]2[CH:9]=[C:2]3[C:3]([C:4]([NH2:5])=[N:30][NH:31]3)=[C:6]([O:27][CH3:28])[CH:7]=2)[CH:15]=[C:14]([N:16]2[CH2:20][CH2:19][CH2:18][C@H:17]2[C:21]([F:22])([F:24])[F:23])[N:13]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 58504597HCID 58504597, compound

Product 1

HCID 58504834HCID 58504834, compoundYield 54.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

2-Fluoro-4-{2-(methylamino)-6-[(2S)-2-(trifluoromethyl)-1-pyrrolidinyl]-4-pyrimidinyl}-6-(methyloxy)benzonitrile (131 mg, 0.331 mmol) was dissolved in ethanol (3 mL) in a 5 mL sealable vial. Hydrazine monohydrate (0.487 mL, 9.94 mmol) was added, the vial was capped, and the reaction was heated at 100° C. overnight. The reaction was concentrated, dissolved in 2 mL of DMSO and purified in HPLC (HPLC condition: open-access Gilson using Trilution software with a Sunfire 5u C18(2) 100A. 50×30.00 mm 5 micron. 7.3-minute run (47 mL/min, 18% CH3CN/H2O, 0.1% TFA to 43% CH3CN/H2O, 0.1% TFA) with UV detection at 254 nm). Product fractions were combined and the volume was reduced to remove most of the CH3CN. To the water left behind was added saturated NaHCO3, then extracted with EtOAc (3×15 mL). The organic was washed with brine, dried over MgSO4, filtered, concentrated, and transferred to a haystack vial. Water (1 mL) was added, and the resulting mixture was freeze dried to afford the title compound (74 mg) as a light yellow solid. LC-MS (ES) m/z=408 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.95-2.03 (m, 2H), 2.05 (bs, 2H), 2.77 (d, J=3.3 Hz, 3H) 3.47 (d, J=8.8 Hz, 1H) 3.62 (d, J=4.6 Hz, 1H), 3.87 (s, 3H), 4.98 (bs, 2H), 5.08 (bs, 1H), 6.39 (bs, 1H), 6.64 (bs, 1H), 6.88 (bs, 1H), 7.43 (bs, 1H), 11.50 (bs, 1H).

Workup

  1. customthe vial was capped
  2. concentrationThe reaction was concentrated
  3. dissolutiondissolved in 2 mL of DMSO
  4. custompurified in HPLC (HPLC condition
  5. custom7.3-minute
  6. customto remove most of the CH3CN
  7. waitTo the water left behind
  8. additionwas added saturated NaHCO3
  9. extractionextracted with EtOAc (3×15 mL)
  10. washThe organic was washed with brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. additionWater (1 mL) was added
  15. customdried

Sources & evidence

ORD record
ord-02b6065935994716a62aa4a7eb85d1af
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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