Dimethylformamide → HCID 71767519, compound

HRID 530217Notes

Reaction equation

HRID 530217 reaction equation
[C:1](Cl)(=[O:5])[C:2](Cl)=O.[CH3:7][N:8]([CH:10]=O)[CH3:9].[NH2:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[N:19]=[CH:18][C:17]([C:23]#[N:24])=[C:16]2[NH:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[CH:28][CH:27]=1.[C:39]([O-])(O)=O.[Na+]>C1COCC1.CN1CCCC1=O>[C:23]([C:17]1[CH:18]=[N:19][C:20]2[C:15]([C:16]=1[NH:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)=[CH:28][CH:27]=1)=[CH:14][C:13]([NH:12][C:1](=[O:5])/[CH:2]=[CH:39]/[CH2:10][N:8]([CH3:7])[CH3:9])=[CH:22][CH:21]=2)#[N:24]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 89852603HCID 89852603, compound

Product 1

HCID 71767519HCID 71767519, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Oxalyl chloride (229 mg, 1.80 mmol, 1.5 eq) was added to a solution of 4-(dimethylamino)-1-ylbut-2-enoicacid hydrochloride (200 mg, 1.2 mmol, 1.0 eq) in THF (4 mL) under ice-water bath. This was followed by the addition of a trace amount of DMF. This solution was stirred at rt for 3 hours before added to a solution of. This solution was then cooled in an ice-water bath, and 6-amino-4-((4-phenoxyphenyl)amino)quinoline-3-carbonitrile (253 mg, 0.72 mmol, 0.6 eq) in N-methylpyrrolidinone (5 mL) was added dropwise. The reaction was allowed warmed to room temperature over 4 hours before poured into saturated aqueous NaHCO3 solution, extracted with EA (3×50 mL). The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product was purified by flash column chromatography in silica gel to give (E)-N-(3-cyano-4-((4-phenoxyphenyl)amino)quinolin-6-yl)-4-(dimethylamino)but-2-enamide (Compound 21) as an off-white solid 39 mg. 1H-NMR (300 MHz, DMSO-d6): δ 8.83 p.p.m. (1H, s), 8.56 (1H, s), 7.97 (1H, d, J=6.6 Hz), 7.85 (1H, m), 7.52 (1H, dd, J=6.6, 1.5 Hz), 7.35 (2H, m), 7.12 (1H, m), 7.07 (5H, m), 7.02 (2H, m), 6.22 (1H, d, J=11.7 Hz), 3.19 (3H, m), 2.38 (6H, s).

Workup

  1. additionbefore added to a solution of
  2. temperatureThis solution was then cooled in an ice-water bath
  3. temperatureThe reaction was allowed warmed to room temperature over 4 hours
  4. extractionextracted with EA (3×50 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe crude product was purified by flash column chromatography in silica gel

Sources & evidence

ORD record
ord-a7a2235b10fa421ea91da3543fa6f066
Source dataset
uspto-grants-2016_05
Patent number
US09353062B2

Reaction notes

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