Methyl chloroformate → [7-[(4-Oxo-1H-quinolin-3-yl)carbonylamino]tetralin-1-yl]aminoformic acid methyl ester

HRID 74113Notes

Reaction equation

HRID 74113 reaction equation
[NH2:1][CH:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([NH:12][C:13]([C:15]3[C:24](=[O:25])[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[NH:17][CH:16]=3)=[O:14])[CH:10]=2)[CH2:5][CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.Cl[C:36]([O:38][CH3:39])=[O:37].N1CCCCC1>CO>[CH3:39][O:38][C:36]([NH:1][CH:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([NH:12][C:13]([C:15]3[C:24](=[O:25])[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[NH:17][CH:16]=3)=[O:14])[CH:10]=2)[CH2:5][CH2:4][CH2:3]1)=[O:37]

Participants

6

Reactant 4

HCID 6586Methyl chloroformateHCID 8082PiperidineHCID 81531DiisopropylethylamineHCID 57567368HCID 57567368, compound

Product 1

HCID 57567332[7-[(4-Oxo-1H-quinolin-3-yl)carbonylamino]tetralin-1-yl]aminoformic acid methyl esterYield 35%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of N-(1-aminotetralin-7-yl)-4-oxo-1H-quinoline-3-carboxamide (273-I) (65 mg, 0.20 mmol) and DIEA (52 μL, 0.29 mmol) in methanol (1 mL) was added methyl chloroformate (22 μL, 0.29 mmol). The reaction was stirred at room temperature for 1 h. LCMS analysis of the reaction mixture showed peaks corresponding to both the single and bis addition products. Piperidine (2 mL) was added and the reaction was stirred overnight after which only the single addition product was observed. The resulting solution was filtered and purified by HPLC (10-99% CH3CN—H2O) to yield the product, [7-[(4-oxo-1H-quinolin-3-yl)carbonylamino]tetralin-1-yl]aminoformic acid methyl ester (159) (27 mg, 35%). HPLC ret. time 2.68 min, 10-99% CH3CN, 5 min run; ESI-MS 392.3 m/z (MH+).

Workup

  1. additionbis addition products
  2. stirringthe reaction was stirred overnight after which only the single addition product
  3. filtrationThe resulting solution was filtered
  4. custompurified by HPLC (10-99% CH3CN—H2O)

Sources & evidence

ORD record
ord-18530ecaa224473eadfe4d40a33eeeef
Source dataset
uspto-grants-2014_09
Patent number
US08829204B2

Reaction notes

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