Ethanol → (3S,6R)-1-[2-Amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamide

HRID 2367444Notes

Reaction equation

HRID 2367444 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][CH2:11][C@H:10]([C:15]([NH:17][CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:24]2[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[C:26](F)[CH:25]=2)[N:3]=1.CCO.CCN(C(C)C)C(C)C.[NH2:45][NH2:46]>CO>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][CH2:11][C@H:10]([C:15]([NH:17][CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:24]2[CH:25]=[C:26]3[C:27]([C:30]([NH2:31])=[N:45][NH:46]3)=[CH:28][CH:29]=2)[N:3]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 51357956(3S,6R)-1-[2-Amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamide

Product 1

HCID 51357954(3S,6R)-1-[2-Amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamideYield 65.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
110 °C

Procedure

Into a microwave tube, (3S,6R)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-N-cyclohexyl-6-methyl-3-piperidinecarboxamide (235 mg, 0.538 mmol), 5 ml of EtOH, Hunig's base (0.376 ml, 2.153 mmol), and hydrazine anhydrous (0.101 mL, 3.23 mmol) were added, and the yellow suspension mixture was heated overnight at 110° C. in an oil bath. When the temperature of the reaction reached 100° C. while heating, the solid in the mixture was all dissolved. After overnight, there were yellow suspension as well as some black colored solid formed. LCMS showed mainly product. The black solid and the yellow solid were carefully separated due to the black solid being heavier than yellow solid in the CH3OH solvent. The yellow solid in CH3OH was filtered and washed with CH3OH to remove the color and afford the title compound (157 mg) as a white solid. LC-MS (ES) m/z=449 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.05-1.35 (m, 8H), 1.50-1.88 (m, 9H), 2.24 (s, 1H), 2.90 (s, 1H), 3.46-3.60 (m, 1H), 5.38 (s, 2H), 6.07 (s, 2H), 6.57 (s, 1H), 7.57 (d, J=8.3 Hz, 1H), 7.70 (d, J=8.3 Hz, 1H), 7.79 (d, J=7.6 Hz, 1H), 7.94 (s, 1H), 11.49 (s, 1H).

Workup

  1. customreached 100° C.
  2. temperaturewhile heating
  3. customformed
  4. filtrationThe yellow solid in CH3OH was filtered
  5. washwashed with CH3OH
  6. customto remove the color

Sources & evidence

ORD record
ord-101faf3a396940a181af8dded4ff9a72
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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