1H-Indazol-5-amine → 5-fluoro-N-1H-indazol-5-ylquinazolin-4-amine

HRID 1162199Notes

Reaction equation

HRID 1162199 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[F:12])[N:5]=[CH:4][N:3]=1.[NH2:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[NH:19][N:18]=[CH:17]2>C(O)(C)C>[F:12][C:10]1[CH:9]=[CH:8][CH:7]=[C:6]2[C:11]=1[C:2]([NH:13][C:14]1[CH:15]=[C:16]3[C:20](=[CH:21][CH:22]=1)[NH:19][N:18]=[CH:17]3)=[N:3][CH:4]=[N:5]2

Participants

4

Reactant 2

HCID 880121H-Indazol-5-amineHCID 119744454-Chloro-5-fluoroquinazoline

Product 1

HCID 686187815-fluoro-N-1H-indazol-5-ylquinazolin-4-amineYield 89%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A stirred partial solution of 4-chloro-5-fluoroquinazoline (10.95 g, 60 mmol) and 5-aminoindazole (7.98 g, 60 mmol) in isopropanol (300 ml) was heated under reflux for 3 hours. On cooling to ambient temperature the product hydrochloride salt was filtered off and washed with isopropanol and ether. The salt was heated with water (400 ml)/ethanol (100 ml) and the partial solution was basified with aqueous ammonia. The precipitated solid was filtered off and washed with water to provide 5-fluoro-N-1H-indazol-5-ylquinazolin-4-amine (14.91 g, 89%); NMR spectrum (300 MHz) 7.42 (dd, 1H), 7.53 (s, 2H), 7.60 (d, 1H), 7.83 (m, 1H), 8.08 (d, 2H), 8.50 (s, 1H), 9.20 (d, 1H), 13.05 (s, 1H); Mass spectrum MH+ 280.

Workup

  1. temperatureunder reflux for 3 hours
  2. filtrationwas filtered off
  3. washwashed with isopropanol and ether
  4. temperatureThe salt was heated with water (400 ml)/ethanol (100 ml)
  5. filtrationThe precipitated solid was filtered off
  6. washwashed with water

Sources & evidence

ORD record
ord-8119eb73870a48d1aec1c4ff90f89a98
Source dataset
uspto-grants-2010_10
Patent number
US07820683B2

Reaction notes

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