1-Hydroxybenzotriazole → HCID 60164711, compound

HRID 2273183Notes

Reaction equation

HRID 2273183 reaction equation
[O:1]=[C:2]1[NH:7][C:6]2[CH:8]=[C:9]([C:12]([OH:14])=O)[CH:10]=[CH:11][C:5]=2[S:4][CH2:3]1.[CH3:15][O:16][C:17]1[CH:18]=[C:19]2[C:28](=[CH:29][CH:30]=1)[N:27]=[CH:26][C:25]1[O:24][CH2:23][CH:22]([N:31]3[CH2:36][CH2:35][CH:34]([NH2:37])[CH2:33][CH2:32]3)[CH2:21][C:20]2=1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH3:15][O:16][C:17]1[CH:18]=[C:19]2[C:28](=[CH:29][CH:30]=1)[N:27]=[CH:26][C:25]1[O:24][CH2:23][CH:22]([N:31]3[CH2:32][CH2:33][CH:34]([NH:37][C: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)=[O:14])[CH2:35][CH2:36]3)[CH2:21][C:20]2=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7609933-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67247410HCID 67247410, compound

Product 1

HCID 60164711HCID 60164711, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-Oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid (31 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 N,N-dimethylformamide (3 mL), followed by 1-hydroxybenzotriazole (21 mg, 0.15 mmol, 1.1 eq), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (31 mg, 0.16 mmol, 1.15 eq) and N,N-diisopropylethylamine (53 μL, 0.31 mmol, 2.25 eq). After 15 hours stirring at room temperature, solvent is evaporated 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 crude product 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-9-aza-phenanthrene-3-yl)-piperidin-4-yl]-amide as an off-white lyophilizated powder (24 mg, 33% yield).

Workup

  1. customsolvent is evaporated
  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 crude product that
  7. customis purified by preparative HPLC

Sources & evidence

ORD record
ord-2c9f933c8dbe47b59f7c8981b08ef969
Source dataset
uspto-grants-2015_09
Patent number
US09120822B2

Reaction notes

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