Benzophenone imine → 2-(6-Amino-2,3-dihydro-4h-1,4-benzoxazin-4-yl)-7,7-dimethyl-5,6,7,8-tetrahydro-4h-[1,3]thiazolo[5,4-c]azepin-4-one

HRID 417940Notes

Reaction equation

HRID 417940 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][CH2:8][N:7]([C:11]3[S:12][C:13]4[C:14](=[O:23])[NH:15][CH2:16][C:17]([CH3:22])([CH3:21])[CH2:18][C:19]=4[N:20]=3)[C:6]=2[CH:24]=1.C(=[NH:38])(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+]>C1COCC1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:38][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][CH2:8][N:7]([C:11]3[S:12][C:13]4[C:14](=[O:23])[NH:15][CH2:16][C:17]([CH3:22])([CH3:21])[CH2:18][C:19]=4[N:20]=3)[C:6]=2[CH:24]=1

Participants

6

Reactant 3

HCID 136809Benzophenone imineHCID 23676156Sodium t-butoxideHCID 666485842-(6-Bromo-2,3-dihydro-4h-1,4-benzoxazin-4-yl)-7,7-dimethyl-5,6,7,8-tetrahydro-4h-[1,3]thiazolo[5,4-c]azepin-4-one

Product 1

HCID 666484122-(6-Amino-2,3-dihydro-4h-1,4-benzoxazin-4-yl)-7,7-dimethyl-5,6,7,8-tetrahydro-4h-[1,3]thiazolo[5,4-c]azepin-4-oneYield 89%

Reagents, catalysts & solvents 2

HCID 634876Binap, (A+-)-CatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of Example 67 (0.48 g, 0.98 mmol), benzophenone imine (0.356 g, 1.96 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (40 mg, 0.06 mmol), sodium tert-butoxide (0.192 g, 2.0 mmol) and tris(dibenzylidineacetone)dipalladium(0) (29 mg, catalytic) in THF (10 mL) was heated to 120° C. for 2 h. The reaction mixture was cooled to r.t., concentrated in vacuo, and the residue dissolved in methanol (2 mL). 2N Hydrochloric acid (10 mL) was added and the mixture stirred overnight. It was basified with aqueous sodium carbonate and extracted with DCM (3×25 mL). The combined organic fractions were dried (MgSO4) and concentrated in vacuo. The residue was triturated with Et2O to give the title compound (0.30 g, 89%) as a beige solid. δH (CDCl3) 1.11 (6H, s), 2.85 (2H, s), 3.12 (2H, d, J 5.3 Hz), 3.52 (2H, br.s), 4.07-4.13 (2H, m), 4.19-4.26 (2H, m), 5.93 (1H, br.s), 6.40 (1H, dd, J 8.5, 2.6 Hz), 6.75 (1H, d, J 8.7 Hz), 7.29 (1H, d, J 2.6 Hz). LCMS (ES+) 345 (M+H)+.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionthe residue dissolved in methanol (2 mL)
  3. addition2N Hydrochloric acid (10 mL) was added
  4. extractionextracted with DCM (3×25 mL)
  5. dry with materialThe combined organic fractions were dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was triturated with Et2O

Sources & evidence

ORD record
ord-b6ed49a86437472c80ae696ac19de7c7
Source dataset
uspto-grants-2012_01
Patent number
US08093238B2

Reaction notes

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