Acetic Acid → HCID 53246013, compound

HRID 2273184Notes

Reaction equation

HRID 2273184 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[S:4][CH2:3]1.[CH3:14][O:15][C:16]1[CH:17]=[C:18]2[C:27](=[CH:28][CH:29]=1)[N:26]=[CH:25][C:24]1[O:23][CH2:22][CH:21]([N:30]3[CH2:35][CH2:34][CH:33]([NH2:36])[CH2:32][CH2:31]3)[CH2:20][C:19]2=1.C(O)(=O)C.C([BH3-])#N.[Na+]>ClCCCl.CO>[CH3:14][O:15][C:16]1[CH:17]=[C:18]2[C:27](=[CH:28][CH:29]=1)[N:26]=[CH:25][C:24]1[O:23][CH2:22][CH:21]([N:30]3[CH2:31][CH2:32][CH:33]([NH:36][CH2:12][C:9]4[CH:10]=[CH:11][C:5]5[S:4][CH2:3][C:2](=[O:1])[NH:7][C:6]=5[CH:8]=4)[CH2:34][CH2:35]3)[CH2:20][C:19]2=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 109433483-Oxo-3,4-dihydro-2H-1,4-benzothiazine-6-carbaldehydeHCID 67247410HCID 67247410, compound

Product 1

HCID 53246013HCID 53246013, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolvent

Procedure

3-Oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carbaldehyde (28 mg, 0.14 mmol 1.0 eq) is added at room temperature to a stirred solution of 1-(6-methoxy-3,4-dihydro-2H-1-oxa-9-aza-phenanthrene-3-yl)-piperidin-4-ylamine (50 mg, 0.14 mmol, 1.0 eq) in 1,2-dichloroethane (3 mL) and methanol (1.5 mL), followed by acetic acid (9 μL, 0.16 mmol, 1.15 eq) and sodium cyanoborohydride (12 mg, 0.18 mmol, 1.3 eq). After 15 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-{[1-(6-methoxy-3,4-dihydro-2H-1-oxa-9-aza-phenanthrene-3-yl)-piperidin-4-ylamino]-methyl}-4H-benzo[1,4]thiazine-3-one as an off-white lyophilizated solid (25 mg, 36% 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-5ac3ee3eb897435e9463889135b0f8ca
Source dataset
uspto-grants-2015_09
Patent number
US09120822B2

Reaction notes

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