Diisopropylethylamine → 3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [1-(6-methoxy-3,4-dihydro-2H-1-oxa-5,9-diaza-phenanthren-3-ylmethyl)-piperidin-4-yl]-amide

HRID 633799Notes

Reaction equation

HRID 633799 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8]([C:10]2[CH:11]=[CH:12][C:13]3[S:18][CH2:17][C:16](=[O:19])[NH:15][C:14]=3[CH:20]=2)=[O:9])[CH2:3][CH2:2]1.Br[CH2:22][CH:23]1[CH2:36][C:35]2[C:34]3[C:29](=[CH:30][CH:31]=[C:32]([O:37][CH3:38])[N:33]=3)[N:28]=[CH:27][C:26]=2[O:25][CH2:24]1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH3:38][O:37][C:32]1[N:33]=[C:34]2[C:29](=[CH:30][CH:31]=1)[N:28]=[CH:27][C:26]1[O:25][CH2:24][CH:23]([CH2:22][N:1]3[CH2:6][CH2:5][CH:4]([NH:7][C:8]([C:10]4[CH:11]=[CH:12][C:13]5[S:18][CH2:17][C:16](=[O:19])[NH:15][C:14]=5[CH:20]=4)=[O:9])[CH2:3][CH2:2]3)[CH2:36][C:35]2=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 711178593-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid piperidin-4-ylamideHCID 867306953-bromomethyl-6-methoxy-3,4-dihydro-2H-1-oxa-5,9-diaza-phenanthrene

Product 1

HCID 714886353-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [1-(6-methoxy-3,4-dihydro-2H-1-oxa-5,9-diaza-phenanthren-3-ylmethyl)-piperidin-4-yl]-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

3-Oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid piperidin-4-ylamide (56 mg, 0.16 mmol, 1.0 eq) is added at room temperature to a stirred solution of 3-bromomethyl-6-methoxy-3,4-dihydro-2H-1-oxa-5,9-diaza-phenanthrene (50 mg, 0.16 mmol, 1.0 eq) in N,N-dimethylformamide (2 mL), followed by N,N-diisopropylethylamine (30 μL, 0.17 mmol, 1.1 eq). After 24 hours stirring at 80° C., solvent is removed and the residue is extracted with dichloromethane (3×10 mL) and water (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 3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [1-(6-methoxy-3,4-dihydro-2H-1-oxa-5,9-diaza-phenanthren-3-ylmethyl)-piperidin-4-yl]-amide as an off-white lyophilized powder (39 mg, 47% yield).

Workup

  1. customsolvent is removed
  2. extractionthe residue is extracted with dichloromethane (3×10 mL) and water (10 mL)
  3. dry with materialThe combined organic layers are dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a residue that
  7. customis purified by preparative HPLC

Sources & evidence

ORD record
ord-19b819287d9f4c31ab2dc5cd57d37751
Source dataset
uspto-grants-2016_04
Patent number
US09321788B2

Reaction notes

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