Ethyl Acetate → 6-{2-Amino-6-[(2R)-2-ethyl-1-pyrrolidinyl]-4-pyrimidinyl}-1H-indazol-3-amine

HRID 2367227Notes

Reaction equation

HRID 2367227 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][C@H:18]2[CH2:22][CH3:23])[N:3]=1.O.[NH2:25][NH2:26].CCOC(C)=O>C(O)C>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[C:10]3[C:11]([C:12]([NH2:13])=[N:25][NH:26]3)=[CH:14][CH:15]=2)[CH:5]=[C:4]([N:17]2[CH2:21][CH2:20][CH2:19][C@H:18]2[CH2:22][CH3:23])[N:3]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 24654Hydrazine hydrate (1:1)HCID 585047884-{2-Amino-6-[(2R)-2-ethyl-1-pyrrolidinyl]-4-pyrimidinyl}-2-fluorobenzonitrile

Product 1

HCID 462164936-{2-Amino-6-[(2R)-2-ethyl-1-pyrrolidinyl]-4-pyrimidinyl}-1H-indazol-3-amineYield 58%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

To 4-{2-amino-6-[(2R)-2-ethyl-1-pyrrolidinyl]-4-pyrimidinyl}-2-fluorobenzonitrile (50 mg, 0.161 mmol) in ethanol (4 mL) was added hydrazine monohydrate (1 mL, 20.40 mmol), and the reaction mixture was stirred overnight at 100° C. into a sealed tube. The reaction was poured onto water and EtOAc, and the organic layer was separated, dried (MgSO4), filtered and concentrated. The resulting solid was dissolved in ethanol (˜2 mL), and treated with hexanes until the solution became cloudy. The mixture was roto-evaporated (˜½ original volume) until a heavy precipitate was observed. The solution was decanted and the solid was dried under vacuum at 40° C. to afford the title compound (30 mg, 58%) as a pale yellow solid. LC-MS (ES) m/z=324 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.89 (t, J=7.3 Hz, 3H), 1.37 (m, 1H), 1.7-2.0 (m, 5H), 3.40 (m, 1H), 3.50 (m, 1H), 4.00 (m, 1H), 5.38 (bs, 2H), 5.97 (bs, 2H), 6.23 (s, 1H), 7.51 (dd, J=8.6, 1.0 Hz, 1H), 7.70 (d, J=8.3 Hz, 1H), 7.89 (s, 1H), 11.49 (s, 1H).

Workup

  1. customthe organic layer was separated
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe resulting solid was dissolved in ethanol (˜2 mL)
  6. additiontreated with hexanes until the solution
  7. customThe mixture was roto-evaporated (˜½ original volume) until a heavy precipitate
  8. customThe solution was decanted
  9. customthe solid was dried under vacuum at 40° C.

Sources & evidence

ORD record
ord-2511ee2d4f7243c89002e56b951b1af7
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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