Diethyl Ether → HCID 59361843, compound

HRID 61675Notes

Reaction equation

HRID 61675 reaction equation
C([O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[C:10]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([NH2:21])[CH:16]=1)[N:9]=[C:8]2[NH:22][C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[N:28]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[N:27]=[CH:26]2)(=O)C.CCN(C(C)C)C(C)C.[C:48](Cl)(=[O:52])[CH2:49][CH2:50][CH3:51].CCOCC>ClCCl>[C:48]([NH:21][C:17]1[CH:16]=[C:15]([C:10]2[N:9]=[C:8]([NH:22][C:23]3[CH:24]=[C:25]4[C:29](=[CH:30][CH:31]=3)[N:28]([C:32]([O:34][C:35]([CH3:36])([CH3:38])[CH3:37])=[O:33])[N:27]=[CH:26]4)[C:7]3[C:12](=[CH:13][CH:14]=[C:5]([OH:4])[CH:6]=3)[N:11]=2)[CH:20]=[CH:19][CH:18]=1)(=[O:52])[CH2:49][CH2:50][CH3:51]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 8855Butyryl chlorideHCID 81531DiisopropylethylamineHCID 59361927HCID 59361927, compound

Product 1

HCID 59361843HCID 59361843, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 5-(6-acetoxy-2-(3-aminophenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate (0.57 g, 1.12 mmol) and DIEA (0.65 g, 5.03 mmol) in dichloromethane (20 mL) was added butryl chloride (0.180 g, 1.69 mmol). The resulting reaction mixture was stirred at room temperature for 4 h. The volatiles were removed under reduced pressure and the residue was triturated with water causing formation of a precipitate. The solid was collected via filtration and dried under vacuum. The solid was suspended in anhydrous methanol (50 mL) and 28% ammonium hydroxide (0.9 mL) was added. The resulting reaction mixture was stirred at room temperature for 24 h. The volatiles were removed under reduced pressure and the residue upon trituration with ether gave tert-butyl 5-(2-(3-butyramidophenyl)-6-hydroxyquinazolin-4-ylamino)-1H-indazole-1-carboxylate (0.354 g, 0.66 mmol, 59% over two steps). HPLC retention time 6.342 min.

Workup

  1. customThe resulting reaction mixture
  2. customThe volatiles were removed under reduced pressure
  3. customthe residue was triturated with water causing formation of a precipitate
  4. filtrationThe solid was collected via filtration
  5. customdried under vacuum
  6. addition28% ammonium hydroxide (0.9 mL) was added
  7. customThe resulting reaction mixture
  8. stirringwas stirred at room temperature for 24 h
  9. customThe volatiles were removed under reduced pressure

Sources & evidence

ORD record
ord-ac28d75447b5481191433004ece62e9b
Source dataset
uspto-grants-2016_09
Patent number
US09440961B2

Reaction notes

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