Dimethylformamide → HCID 68464792, compound

HRID 1915517Notes

Reaction equation

HRID 1915517 reaction equation
[C:1](=[O:31])([O:29][CH3:30])[O:2][C:3]1[CH:8]=[C:7]([NH:9][C:10]([C:12]2[C:21](=[O:22])[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[NH:14][CH:13]=2)=[O:11])[C:6](Br)=[CH:5][C:4]=1[CH:24]1[CH2:28][CH2:27][CH2:26][CH2:25]1.CN(C=O)C.[CH2:37]([OH:40])[C:38]#[CH:39]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(N(CC)CC)C>[C:1](=[O:31])([O:29][CH3:30])[O:2][C:3]1[CH:8]=[C:7]([NH:9][C:10]([C:12]2[C:21](=[O:22])[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[NH:14][CH:13]=2)=[O:11])[C:6]([C:39]#[C:38][CH2:37][OH:40])=[CH:5][C:4]=1[CH:24]1[CH2:28][CH2:27][CH2:26][CH2:25]1.[CH:24]1([C:4]2[C:3]([OH:2])=[CH:8][C:7]([NH:9][C:10]([C:12]3[C:21](=[O:22])[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[NH:14][CH:13]=3)=[O:11])=[C:6]([C:39]#[C:38][CH2:37][OH:40])[CH:5]=2)[CH2:28][CH2:27][CH2:26][CH2:25]1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 7859Propargyl alcoholHCID 59410076HCID 59410076, compound

Product 1

HCID 68464792HCID 68464792, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
80 °C

Procedure

4-bromo-2-cyclopentyl-5-(4-oxo-1,4-dihydroquinoline-3-carboxamido)phenyl methyl carbonate (50 mg, 0.10 mmol), Pd(PPh3)2Cl2 (4 mg, 0.005 mmol), and cuprous iodide (1 mg, 0.10 μL, 0.003 mmol) were added to a microwave tube which was flushed with N2 and capped. A degassed solution of DMF (1 mL), triethylamine (2 mL), and prop-2-yn-1-ol (57.75 mg, 59.97 μL, 1.030 mmol) was added and the reaction mixture was heated at 80° C. for 16 h. The reaction mixture was filtered and purified by HPLC (20-99% CH3CN/0.05% TFA) to give 2-cyclopentyl-4-(3-hydroxyprop-1-ynyl)-5-(4-oxo-1,4-dihydroquinoline-3-carboxamido)phenyl methyl carbonate/N-(4-cyclopentyl-5-hydroxy-2-(3-hydroxyprop-1-ynyl)phenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide. These product fractions were combined, concentrated to remove acetonitrile, and treated with 5N NaOH (2 mL). The pH of the solution was adjusted to 7 and the reaction mixture was extracted with ethyl acetate. The organic layer was washed with 50% saturated sodium bicarbonate solution (2×20 mL) and brine. The solution was dried over anhydrous Na2SO4, filtered, and dried to obtain N-(4-cyclopentyl-5-hydroxy-2-(3-hydroxyprop-1-ynyl)phenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide. LC/MS: m/z 403.2 (M+H)+ at 0.92 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. customwas flushed with N2
  2. customcapped
  3. filtrationThe reaction mixture was filtered
  4. custompurified by HPLC (20-99% CH3CN/0.05% TFA)

Sources & evidence

ORD record
ord-c1fe8d8ca8574efeb8911b3e33107de5
Source dataset
uspto-grants-2013_12
Patent number
US08614327B2

Reaction notes

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