4-Methylmorpholine → HCID 23630103, compound

HRID 2375628Notes

Reaction equation

HRID 2375628 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([C:12]3[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=3)[C:15]([OH:17])=O)[CH:8]=[CH:9][CH:10]=2)[N:5]=[N:4][C:3]=1[C:21](=[O:26])[NH:22][CH2:23][CH2:24][CH3:25].[NH:27]1[CH2:30][CH2:29][CH2:28]1.CN1CCOCC1.ON1C2C=CC=CC=2N=N1>CN(C=O)C.O>[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([C:12]3[CH:20]=[CH:19][CH:18]=[C:14]([C:15]([N:27]4[CH2:30][CH2:29][CH2:28]4)=[O:17])[CH:13]=3)[CH:8]=[CH:9][CH:10]=2)[N:5]=[N:4][C:3]=1[C:21]([NH:22][CH2:23][CH2:24][CH3:25])=[O:26]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 10422AzetidineHCID 757711-HydroxybenzotriazoleHCID 23630102HCID 23630102, compound

Product 1

HCID 23630103HCID 23630103, compoundYield 82%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 3-[4-amino-3-(propylcarbamoyl)cinnolin-8-yl]benzoic acid (67 mg, 0.191 mmol) dissolved in anhydrous DMF (2 mL) at ambient temperature under argon was added azetidine (16.4 mg, 0.287 mmol), N-methylmorpholine (29 mg, 0.287 mmol), 1-hydroxybenzotriazole (44 mg, 0.287 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcabodiimide hydrochloride (55 mg, 0.287 mmol). The mixture was stirred at ambient temperature for 19 hours then diluted with water and extracted with ethyl acetate. The residue from the organic extracts was purified by flash chromatography on silica gel eluting with increasingly polar gradient of ethyl acetate in hexanes to afford the title compound (61 mg, 82% yield) as a white solid. 1H NMR (300 MHz, CDCl3) δ 8.54 (br, 1H), 8.03-7.64 (m, 6H), 7.53 (t, J=7.7 Hz, 1H), 4.38 (br, 2H), 4.25 (br, 2H), 3.47 (apparent quartet, J=7.0 Hz, 2H), 2.34 (apparent pentet, J=7.5 Hz, 2H), 1.67 (apparent sextet, J=7.0 Hz, 2H), 1.01 (t, J=7.4 Hz, 3H) MS APCI, m/z=390 (M+H) HPLC 1.70 min.

Workup

  1. extractionextracted with ethyl acetate
  2. customThe residue from the organic extracts was purified by flash chromatography on silica gel eluting
  3. temperaturewith increasingly polar gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-fc26d869518e477bb02bd5e7db030644
Source dataset
uspto-grants-2008_12
Patent number
US07465795B2

Reaction notes

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