Hydrochloric Acid → 5-fluoro-N-[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]quinazolin-4-amine

HRID 1162212Notes

Reaction equation

HRID 1162212 reaction equation
Cl.O1CCOCC1.[N:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][N:15]1[C:23]2[C:18](=[CH:19][C:20]([NH2:24])=[CH:21][CH:22]=2)[CH:17]=[N:16]1.Cl[C:26]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][C:34]=2[F:36])[N:29]=[CH:28][N:27]=1>C(#N)C>[F:36][C:34]1[CH:33]=[CH:32][CH:31]=[C:30]2[C:35]=1[C:26]([NH:24][C:20]1[CH:19]=[C:18]3[C:23](=[CH:22][CH:21]=1)[N:15]([CH2:14][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][N:8]=1)[N:16]=[CH:17]3)=[N:27][CH:28]=[N:29]2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 119744454-Chloro-5-fluoroquinazolineHCID 219523661-(Pyridin-2-ylmethyl)-1H-indazol-5-amine

Product 1

HCID 686183205-fluoro-N-[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]quinazolin-4-amineYield 72%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

4N Hydrogen chloride in dioxane (9.6 ml, 38.4 mmol) was added to a mixture of 1-(pyridin-2-ylmethyl)-1H-indazol-5-amine (8.78 g, 39.2 mmol) and 4-chloro-5-fluoroquinazoline (7 g, 38.4 mmol; prepared as described in WO 2001/094341) in acetonitrile (100 ml). The mixture was stirred at 75° C. for 1.5 hours. After cooling, the mixture was evaporated to dryness. The residue was diluted in 6N methanolic ammonia. The mixture was evaporated to dryness and was diluted in DCM. After filtration of the solids, the filtrate was evaporated to dryness. The residue was purified by chromatography on silica gel (eluant: methanol in DCM) to give 5-fluoro-N-[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]quinazolin-4-amine as a beige solid (10.2 g, 72%); NMR spectrum (CDCl3) 5.76 (s, 2H), 6.89 (d, 1H), 7.22-7.18 (m, 2H), 7.58-7.45 (m, 3H), 7.72 (m, 2H), 8.11 (s, 1H), 8.21 (s, 1H), 8.47 (m, 1H), 8.60 (d, 1H), 8.68 (s, 1H); Mass spectrum MH+ 371.

Workup

  1. temperatureAfter cooling
  2. customthe mixture was evaporated to dryness
  3. additionThe residue was diluted in 6N methanolic ammonia
  4. customThe mixture was evaporated to dryness
  5. additionwas diluted in DCM
  6. filtrationAfter filtration of the solids
  7. customthe filtrate was evaporated to dryness
  8. customThe residue was purified by chromatography on silica gel (eluant: methanol in DCM)

Sources & evidence

ORD record
ord-293fb9e4e9e043db96400696b4c6a2c4
Source dataset
uspto-grants-2010_10
Patent number
US07820683B2

Reaction notes

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