Hydrazine hydrate (1:1) → 6-{2-(Methylamino)-6-[(3R)-3-(1-methylethyl)-4-morpholinyl]-4-pyrimidinyl}-4-(methyloxy)-1H-indazol-3-amine

HRID 2367509Notes

Reaction equation

HRID 2367509 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[CH:22]([CH3:24])[CH3:23])[N:13]=[C:12]([NH:25][CH3:26])[N:11]=2)[CH:7]=[C:6]([O:27][CH3:28])[C:3]=1[C:4]#[N:5].O.[NH2:30][NH2:31]>C(O)C>[CH3:26][NH:25][C:12]1[N:11]=[C:10]([C:8]2[CH:9]=[C:2]3[C:3]([C:4]([NH2:5])=[N:30][NH:31]3)=[C:6]([O:27][CH3:28])[CH:7]=2)[CH:15]=[C:14]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][C@H:17]2[CH:22]([CH3:23])[CH3:24])[N:13]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 585047242-Fluoro-4-{2-(methylamino)-6-[(3R)-3-(1-methylethyl)-4-morpholinyl]-4-pyrimidinyl}-6-(methyloxy)benzonitrile

Product 1

HCID 585046366-{2-(Methylamino)-6-[(3R)-3-(1-methylethyl)-4-morpholinyl]-4-pyrimidinyl}-4-(methyloxy)-1H-indazol-3-amine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-fluoro-4-{2-(methylamino)-6-[(3R)-3-(1-methylethyl)-4-morpholinyl]-4-pyrimidinyl}-6-(methyloxy)benzonitrile (350 mg, 0.91 mmol) in ethanol (10 mL) was added hydrazine monohydrate (2.5 mL) in one portion. The mixture was heated at 100° C. for 20 hours, cooled to room temperature and concentrated in vacuo. The residue was taken up in water (10 mL) as a suspension. The solids were collected by filtration, washed with water (2×2 mL), and dried under vacuum at room temperature over P2O5 for 20 hours. The solids were washed with hexane (2×3 mL). Drying under vacuum at 65° C. for 20 hours afforded the title compound (302 mg) as a cream-colored solid. LC-MS (ES) m/z=398 [M+H]+. 1H NMR (400 MHz, CD3OD): δ 0.89 (d, J=6.8 Hz, 3H), 1.11 (d, J=6.6 Hz, 3H), 2.45-2.55 (m, 1H), 2.96 (s, 3H), 3.25-3.35 (m, 1H), 3.53-3.61 (m, 2H), 3.94 (dd, J=11.1, 3.5 Hz, 1H), 4.04 (s, 3H), 4.11 (d, J=11.9 Hz, 1H), 6.38 (s, 1H), 6.89 (s, 1H), 7.35 (s, 1H).

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated in vacuo
  3. filtrationThe solids were collected by filtration
  4. washwashed with water (2×2 mL)
  5. dry with materialdried under vacuum at room temperature over P2O5 for 20 hours
  6. washThe solids were washed with hexane (2×3 mL)
  7. customDrying under vacuum at 65° C. for 20 hours

Sources & evidence

ORD record
ord-da1a6316031f4d2ab532788ca5a0d744
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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