Acetic Acid → 2H-1,4-benzoxazin-3(4H)-one

HRID 1422756Notes

Reaction equation

HRID 1422756 reaction equation
[O:1]=[C:2]1[NH:7][C:6]2[CH:8]=[C:9](C=O)[CH:10]=[CH:11][C:5]=2[O:4][CH2:3]1.COC1C=C2C(N=CC(SCCN3CCC(N)CC3)=N2)=CC=1.C(O)(=O)C.C([BH3-])#N.[Na+]>ClCCCl.CO>[O:4]1[C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[NH:7][C:2](=[O:1])[CH2:3]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 107736383-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carbaldehydeHCID 667465301-[2-(7-Methoxy-quinoxalin-2-ylsulfanyl)-ethyl]-piperidin-4-ylamine

Product 1

HCID 727572H-1,4-benzoxazin-3(4H)-oneYield 167.6%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolvent

Procedure

3-Oxo-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbaldehyde (354 mg, 2.00 mmol, 1.0 eq) is added at room temperature to a stirred solution of 1-[2-(7-methoxy-quinoxalin-2-ylsulfanyl)-ethyl]-piperidin-4-ylamine (0.65 g, 2.00 mmol, 1.0 eq) in 1,2-dichloroethane (4 mL) and methanol (1 mL), followed by acetic acid (0.11 mL, 2.00 mmol, 1.0 eq) and sodium cyanoborohydride (160 mg, 2.6 mmol, 1.4 eq). After 15 hours stirring at room temperature, the reaction mixture is extracted with dichloromethane (3×20 mL) and a saturated sodium hydrogen carbonate aqueous solution (20 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is purified by preparative HPLC to afford 6-({1-[2-(7-methoxy-quinoxalin-2-ylsulfanyl)-ethyl]-piperidin-4-yl}-amino)-methyl)-4H-benzo[1,4]oxazin-3-one as a white solid (500 mg, 52% yield).

Workup

  1. extractionthe reaction mixture is extracted with dichloromethane (3×20 mL)
  2. dry with materialThe combined organic layers are dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a residue that
  6. customis purified by preparative HPLC

Sources & evidence

ORD record
ord-64fe74c041344b4b94648cc83a86a94e
Source dataset
uspto-grants-2015_01
Patent number
US08927542B2

Reaction notes

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