Ethanol → 4-Fluoro-6-{2-(methylamino)-6-[(3R)-3-methyl-4-morpholinyl]-4-pyrimidinyl}-1H-indazol-3-amine

HRID 2367535Notes

Reaction equation

HRID 2367535 reaction equation
F[C:2]1[CH:9]=[C:8]([C:10]2[CH:15]=[C:14]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][C@H:17]3[CH3:22])[N:13]=[C:12]([NH:23][CH3:24])[N:11]=2)[CH:7]=[C:6]([F:25])[C:3]=1[C:4]#[N:5].[NH2:26][NH2:27].CCN(C(C)C)C(C)C.C(O)C>O.CCOC(C)=O>[F:25][C:6]1[CH:7]=[C:8]([C:10]2[CH:15]=[C:14]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][C@H:17]3[CH3:22])[N:13]=[C:12]([NH:23][CH3:24])[N:11]=2)[CH:9]=[C:2]2[C:3]=1[C:4]([NH2:5])=[N:26][NH:27]2

Participants

7

Reactant 4

HCID 702EthanolHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 585047102,6-Difluoro-4-{2-(methylamino)-6-[(3R)-3-methyl-4-morpholinyl]-4-pyrimidinyl}benzonitrile

Product 1

HCID 462151264-Fluoro-6-{2-(methylamino)-6-[(3R)-3-methyl-4-morpholinyl]-4-pyrimidinyl}-1H-indazol-3-amineYield 68.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

A 2-mL microwave vial was charged with 2,6-difluoro-4-{2-(methylamino)-6-[(3R)-3-methyl-4-morpholinyl]-4-pyrimidinyl}benzonitrile (75 mg, 0.217 mmol), hydrazine (0.027 mL, 0.869 mmol), Hunig's base (0.152 mL, 0.869 mmol) and ethanol (1 mL). The reaction mixture was heated at 150° C. for 15 minutes in a microwave reactor. The reaction mixture was allowed to cool, then was poured into EtOAc (50 mL) and water (25 mL). The aqueous layer was extracted with two further portion of EtOAc (2×50 mL), and the combined organics dried over Na2SO4. The dried solution was filtered and concentrated, and the resulting residue was purified by RP-HPLC (0-30% CH3CN in H2O, 0.1% TFA) to afford the title compound (53.2 mg) as a yellow solid. LC-MS (ES) m/z=358 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.19 (d, J=6.6 Hz, 3H), 2.83 (bs, 3H), 3.06-3.20 (m, 1H), 3.40-3.52 (m, 1H), 3.55-3.66 (m, 1H), 3.69-3.78 (m, 1H), 3.88-4.00 (m, 1H), 4.06-4.24 (m, 1H), 4.43-4.62 (m, 1H), 5.27 (bs, 2H), 6.45-6.71 (m, 2H), 7.26-7.49 (m, 1H), 7.76-7.96 (m, 1H), 11.71-12.13 (m, 1H).

Workup

  1. temperatureto cool
  2. extractionThe aqueous layer was extracted with two further portion of EtOAc (2×50 mL)
  3. dry with materialthe combined organics dried over Na2SO4
  4. filtrationThe dried solution was filtered
  5. concentrationconcentrated
  6. customthe resulting residue was purified by RP-HPLC (0-30% CH3CN in H2O, 0.1% TFA)

Sources & evidence

ORD record
ord-8eb2e9a9bcbe4737acd9d0e648471ade
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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