Hydrazine → HCID 58504699, compound

HRID 2367539Notes

Reaction equation

HRID 2367539 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]([S:25][CH3:26])[C:3]=1[C:4]#[N:5].[NH2:27][NH2:28].CCN(C(C)C)C(C)C>C(O)C>[CH3:24][NH:23][C:12]1[N:11]=[C:10]([C:8]2[CH:9]=[C:2]3[C:3]([C:4]([NH2:5])=[N:27][NH:28]3)=[C:6]([S:25][CH3:26])[CH:7]=2)[CH:15]=[C:14]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][C@H:17]2[CH3:22])[N:13]=1

Participants

5

Reactant 3

HCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 58504418HCID 58504418, compound

Product 1

HCID 58504699HCID 58504699, compoundYield 67.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
150 °C

Procedure

A 2-mL microwave vial was charged with 2-fluoro-4-{2-(methylamino)-6-[(3R)-3-methyl-4-morpholinyl]-4-pyrimidinyl}-6-(methylthio)benzonitrile (40 mg, 0.107 mmol), hydrazine (0.037 mL, 0.643 mmol), Hunig's base (0.056 mL, 0.321 mmol) and ethanol (1.5 mL). The mixture was heated at 150° C. for 90 minutes in a microwave reactor. The reaction mixture was allowed to cool, and then concentrated. The resulting residue was dissolved in DMSO and purified by RP-HPLC (0-30% CH3CN in H2O, 0.1% TFA). The product fractions were pooled, basified with NaHCO3, then extracted into EtOAc. The organic layer was dried, then concentrated to afford the title compound (28 mg) as an off-white solid. LC-MS (ES) m/z=386 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.19 (d, J=6.8 Hz, 3H), 2.61 (s, 3H), 2.83 (d, J=4.3 Hz, 3H), 3.04-3.22 (m, 1H), 3.40-3.52 (m, 1H), 3.55-3.66 (m, 1H), 3.67-3.79 (m, 1H), 3.85-3.99 (m, 1H), 4.05-4.23 (m, 1H), 4.44-4.59 (m, 1H), 5.10 (s, 2H), 6.38-6.71 (m, 2H), 7.26-7.49 (m, 1H), 7.66-7.88 (m, 1H), 11.62-11.92 (m, 1H).

Workup

  1. temperatureto cool
  2. concentrationconcentrated
  3. dissolutionThe resulting residue was dissolved in DMSO
  4. custompurified by RP-HPLC (0-30% CH3CN in H2O, 0.1% TFA)
  5. extractionextracted into EtOAc
  6. customThe organic layer was dried
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-92140a1784c147caa05570ef19d1d374
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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