Dimethylformamide → HCID 66748126, compound

HRID 2401898Notes

Reaction equation

HRID 2401898 reaction equation
[H-].[Na+].CN(C)C=O.[OH:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]=[CH:11][N:10]=1.Br[CH2:20][C:21]1[C:25]([C:26]#[N:27])=[C:24]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[S:23][C:22]=1[C:34]([O:36][CH3:37])=[O:35]>CO.C(Cl)Cl>[C:26]([C:25]1[C:21]([CH2:20][N:10]2[C:9](=[O:8])[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]=[CH:11]2)=[C:22]([C:34]([O:36][CH3:37])=[O:35])[S:23][C:24]=1[N:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1)#[N:27]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 66748038HCID 66748038, compoundHCID 178517962HCID 178517962, compound

Product 1

HCID 66748126HCID 66748126, compoundYield 87.4%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

Under N2 atmosphere Sodium hydride (23.0 mg, 0.910 mmol) was suspended in anhydrous N,N-Dimethylformamide (3.0 mL, 39 mmol), cooled with ice bath and stirred for 10 min. 4-hydroxyquinazoline (0.120 g, 0.821 mmol) was added and the clear solution was stirred at r.t. for 10 min, cooled with ice bath. Methyl 3-(bromomethyl)-4-cyano-5-(morpholin-4-yl)thiophene-2-carboxylate (0.203 g, 0.588 mmol) was added and the reddish-brown solution was stirred with cooling for 40 min. The mixture was quenched with saturated NH4Cl aqueous solution, extracted with EtOAc. The EtOAc solution was washed with water (3×) then brine, dried over Na2SO4, filtered, rotavaped to give a crude solid. Chromatograph in a silica gel column using MeOH/DCM (0/100 to 5/95) afforded a solid product (0.211 g, yield 87.4%). LC/MS: (FA) ES+ 411. 1H NMR (400 MHz, d-chloroform) δ 8.30 (m, 1H), 8.26 (s, 1H), 7.68-7.76 (m, 2H), 7.45-7.49 (m, 1H), 5.43 (s, 2H), 3.83-3.85 (m, 4H), 3.82 (s, 3H), 3.59-3.62 (m, 4H).

Workup

  1. temperaturecooled with ice bath
  2. stirringthe clear solution was stirred at r.t. for 10 min
  3. temperaturecooled with ice bath
  4. stirringthe reddish-brown solution was stirred
  5. temperaturewith cooling for 40 min
  6. customThe mixture was quenched with saturated NH4Cl aqueous solution
  7. extractionextracted with EtOAc
  8. washThe EtOAc solution was washed with water (3×)
  9. dry with materialbrine, dried over Na2SO4
  10. filtrationfiltered
  11. customto give a crude solid

Sources & evidence

ORD record
ord-cc3976b1627f42529036883e32b5608e
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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