Hydrazine hydrate (1:1) → 2-(2-amino-5-hydrazonomethyl-6-methylsulfanyl-pyrimidin-4-ylamino)-N-(3-trifluoromethyl-phenyl)-acetamide

HRID 1160114Notes

Reaction equation

HRID 1160114 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=2)=[O:11])[C:5]([CH:23]=O)=[C:4]([S:25][CH3:26])[N:3]=1.O.[NH2:28][NH2:29]>C(O)(C)C>[NH2:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=2)=[O:11])[C:5]([CH:23]=[N:28][NH2:29])=[C:4]([S:25][CH3:26])[N:3]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 11176608HCID 11176608, compound

Product 1

HCID 668603832-(2-amino-5-hydrazonomethyl-6-methylsulfanyl-pyrimidin-4-ylamino)-N-(3-trifluoromethyl-phenyl)-acetamideYield 45.1%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

To a disposable sealed tube was added 2-(2-amino-5-formyl-6-methylsulfanyl-pyrimidin-4-ylamino)-N-(3-trifluoromethyl-phenyl)-acetamide (100 mg, 0.25 mmol, 1.0 eq.), isopropanol (4.0 mL), and hydrazine monohydrate (0.048 mL, 0.96 mmol, 3.8 eq.). The tube was sealed and heated to 80° C. overnight. The reaction was then quenched with H2O (10 mL) and EtOAc (50 mL). The EtOAc layer washed with brine, dried with Na2SO4, and concentrated to give crude 2-(2-amino-5-hydrazonomethyl-6-methylsulfanyl-pyrimidin-4-ylamino)-N-(3-trifluoromethyl-phenyl)-acetamide as an oil. The crude product was then precipitated out with 3 mL water and 0.5 mL of ACN, filtered and rinsed with 2 mL of H2O to give pure 2-(2-amino-5-hydrazonomethyl-6-methylsulfanyl-pyrimidin-4-ylamino)-N-(3-trifluoromethyl-phenyl)-acetamide as a yellow solid (45.0 mg, 45%). LC/MSD (HP Series 1100 MSD): Expected MW: 399, Observed M+H, 400.1, Retention time: 1.43 min. ANALYTICAL HPLC: >90%, Retention time: 3.89 min (8 minute run). 1H-NMR (d6-DMSO): 10.42 (s, 1H), 9.15 (t, 1H), 8.15 (s, 1H), 8.05 (s, 1H), 7.80 (d, 1H), 7.58 (t, 1H), 7.42 (d, 1H), 6.45 (s, 2H), 5.25 (br s, 2H), 4.30 (d, 2H), 2.40 (s, 3H) ppm.

Workup

  1. customThe tube was sealed
  2. customThe reaction was then quenched with H2O (10 mL) and EtOAc (50 mL)
  3. washThe EtOAc layer washed with brine
  4. dry with materialdried with Na2SO4
  5. concentrationconcentrated
  6. customto give crude 2-(2-amino-5-hydrazonomethyl-6-methylsulfanyl-pyrimidin-4-ylamino)-N-(3-trifluoromethyl-phenyl)-acetamide as an oil
  7. customThe crude product was then precipitated out with 3 mL water and 0.5 mL of ACN
  8. filtrationfiltered
  9. washrinsed with 2 mL of H2O

Sources & evidence

ORD record
ord-e68d1764f79046a68aff04cecbb168f4
Source dataset
uspto-grants-2010_10
Patent number
US07816353B2

Reaction notes

Loading…