Ethyl Acetate → 5-[4-(6,6-Dimethyl-5,6,7,8-tetrahydroquinazolin-4-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl]-3-nitropyridin-2-amine

HRID 241225Notes

Reaction equation

HRID 241225 reaction equation
Cl.Cl.[N+:3]([C:6]1[C:7]([NH2:23])=[N:8][CH:9]=[C:10]([C:12]2[CH:13]=[CH:14][C:15]3[O:21][CH2:20][CH2:19][NH:18][CH2:17][C:16]=3[CH:22]=2)[CH:11]=1)([O-:5])=[O:4].Cl[C:25]1[C:34]2[CH2:33][C:32]([CH3:36])([CH3:35])[CH2:31][CH2:30][C:29]=2[N:28]=[CH:27][N:26]=1.C(N(C(C)C)CC)(C)C.C(OCC)(=O)C>CN1CCCC1=O>[CH3:35][C:32]1([CH3:36])[CH2:31][CH2:30][C:29]2[N:28]=[CH:27][N:26]=[C:25]([N:18]3[CH2:17][C:16]4[CH:22]=[C:12]([C:10]5[CH:11]=[C:6]([N+:3]([O-:5])=[O:4])[C:7]([NH2:23])=[N:8][CH:9]=5)[CH:13]=[CH:14][C:15]=4[O:21][CH2:20][CH2:19]3)[C:34]=2[CH2:33]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 668206213-Nitro-5-(2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)pyridin-2-amine dihydrochlorideHCID 866478114-Chloro-6,6-dimethyl-5,6,7,8-tetrahydroquinazoline

Product 1

HCID 668203605-[4-(6,6-Dimethyl-5,6,7,8-tetrahydroquinazolin-4-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl]-3-nitropyridin-2-amineYield 81.7%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 3-nitro-5-(2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)pyridin-2-amine dihydrochloride (540 mg, 1.50 mmol), 4-chloro-6,6-dimethyl-5,6,7,8-tetrahydroquinazoline (270 mg, 1.37 mmol, reagent preparation 3), and diisopropylethylamine (970 mg, 7.49 mmol) in N-methylpyrrolidinone (3 mL) was stirred at 120° C. for 18 h. After cooling to room temperature ethyl acetate (100 mL) was added, the formed precipitate was filtered off, the organic filtrate was washed with saturated sodium bicarbonate (50 mL), water (2×50 mL), and brine (50 mL), dried over sodium sulfate, filtered and concentrated to afford crude 5-[4-(6,6-dimethyl-5,6,7,8-tetrahydroquinazolin-4-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl]-3-nitropyridine-2-amine (0.5 g) as a brown solid which was used in the next step without further purification. MS (EI) for C24H26N6O3: 447 (MH+).

Workup

  1. additionwas added
  2. filtrationthe formed precipitate was filtered off
  3. washthe organic filtrate was washed with saturated sodium bicarbonate (50 mL), water (2×50 mL), and brine (50 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-63be500c902b4c31a6552d488e01ab8f
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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