Hydrazine hydrate (1:1) → 6-{2-Amino-6-[2-(trifluoromethyl)-1-pyrrolidinyl]-4-pyrimidinyl}-1H-indazol-3-amine

HRID 2367281Notes

Reaction equation

HRID 2367281 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10](F)[CH:9]=2)[CH:5]=[C:4]([N:17]2[CH2:21][CH2:20][CH2:19][CH:18]2[C:22]([F:25])([F:24])[F:23])[N:3]=1.O.[NH2:27][NH2:28]>C(O)C>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:15]=[C:14]3[C:11]([C:12]([NH2:13])=[N:27][NH:28]3)=[CH:10][CH:9]=2)[CH:5]=[C:4]([N:17]2[CH2:21][CH2:20][CH2:19][CH:18]2[C:22]([F:25])([F:24])[F:23])[N:3]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 585045294-{2-Amino-6-[2-(trifluoromethyl)-1-pyrrolidinyl]-4-pyrimidinyl}-2-fluorobenzonitrile

Product 1

HCID 462159936-{2-Amino-6-[2-(trifluoromethyl)-1-pyrrolidinyl]-4-pyrimidinyl}-1H-indazol-3-amineYield 68%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

4-{2-Amino-6-[2-(trifluoromethyl)-1-pyrrolidinyl]-4-pyrimidinyl}-2-fluorobenzonitrile (60 mg, 0.17 mmol) was disolved in ethanol (1.5 mL) with stirring in a 5 mL microwave vessel. Hydrazine monohydrate (0.207 mL, 4.27 mmol) was added, and the mixture was capped and heated at 100° C. in an oil bath overnight. HPLC showed complete conversion. The hot mixture was filtered through a 0.2 um filter disc, rinsing with ethanol (1 mL). Water (˜3 mL) was added to the filtrate with stirring, and the mixture was heated to evaporate most of the ethanol to a volume of ˜4 mL. The mixture was allowed to cool with stirring to room temperature, at which time some product had precipitated as a gum. Stirring was continued for approximately one hour and the precipitate became a free flowing white solid, which was filtered, washed with water and dried to afford the title compound (42 mg) as an off-white solid. LC-MS (ES) m/z=364 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.98-2.08 (m, 2H), 2.08-2.23 (m, 2H), 3.49-3.60 (m, 1H), 3.60-3.72 (m, 1H), 5.06-5.17 (m, 1H), 5.39 (s, 2H), 6.22 (s, 2H), 6.52 (s, 1H), 7.57 (d, J=8.6 Hz, 1H), 7.73 (d, J=8.6 Hz, 1H), 7.94 (s, 1H), 11.54 (s, 1H).

Workup

  1. customthe mixture was capped
  2. filtrationThe hot mixture was filtered through a 0.2 um
  3. filtrationfilter disc
  4. washrinsing with ethanol (1 mL)
  5. additionWater (˜3 mL) was added to the filtrate
  6. stirringwith stirring
  7. temperaturethe mixture was heated
  8. customto evaporate most of the ethanol to a volume of ˜4 mL
  9. temperatureto cool
  10. stirringwith stirring to room temperature, at which time some product
  11. customhad precipitated as a gum
  12. stirringStirring
  13. filtrationwas filtered
  14. washwashed with water
  15. customdried

Sources & evidence

ORD record
ord-afe114931c8d4178905fa40b6b7a325b
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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