Acetic Acid → HCID 178487803, compound

HRID 633812Notes

Reaction equation

HRID 633812 reaction equation
[O:1]=[C:2]1[NH:7][C:6]2[CH:8]=[C:9]([CH:12]=O)[CH:10]=[CH:11][C:5]=2[O:4][CH2:3]1.[CH3:14][O:15][C:16]1[CH:17]=[CH:18][C:19]2[C:24]([N:25]=1)=[C:23]1[CH2:26][CH:27]([CH2:29][C@H:30]3[CH2:35][CH2:34][C@H:33]([NH2:36])[CH2:32][CH2:31]3)[O:28][C:22]1=[CH:21][N:20]=2.C(O)(=O)C.C([BH3-])#N.[Na+]>ClCCCl.CO>[CH3:14][O:15][C:16]1[CH:17]=[CH:18][C:19]2[C:24]([N:25]=1)=[C:23]1[CH2:26][CH:27]([CH2:29][C@H:30]3[CH2:35][CH2:34][C@H:33]([NH:36][CH2:12][C:9]4[CH:10]=[CH:11][C:5]5[O:4][CH2:3][C:2](=[O:1])[NH:7][C:6]=5[CH:8]=4)[CH2:32][CH2:31]3)[O:28][C:22]1=[CH:21][N:20]=2

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 107736383-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carbaldehydeHCID 178487802HCID 178487802, compound

Product 1

HCID 178487803HCID 178487803, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolvent

Procedure

3-Oxo-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbaldehyde (27 mg, 0.14 mmol, 1.0 eq) is added at room temperature to a stirred solution of trans-4-(8-methoxy-1,2-dihydro-3-oxa-5,9-diaza-cyclopenta[a]naphthalen-2-ylmethyl)-cyclohexylamine (47 mg, 0.14 mmol, 1.0 eq) in 1,2-dichloroethane (4 mL) and methanol (1 mL), followed by acetic acid (11 μL, 0.19 mmol, 1.3 eq) and sodium cyanoborohydride (11 mg, 0.16 mmol, 1.15 eq). After 5 hours stirring at room temperature, the reaction mixture is extracted with dichloromethane (3×10 mL) and a saturated sodium hydrogen carbonate aqueous solution (10 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-{[trans-4-(8-methoxy-1,2-dihydro-3-oxa-5,9-diaza-cyclopenta[a]naphthalen-2-ylmethyl)-cyclohexylamino]-methyl}-4H-benzo[1,4]oxazin-3-one as a white lyophilized powder (13 mg, 18% yield).

Workup

  1. extractionthe reaction mixture is extracted with dichloromethane (3×10 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-31ffafcb6de2464d9a8b70da9be520de
Source dataset
uspto-grants-2016_04
Patent number
US09321788B2

Reaction notes

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