Dimethylformamide dimethyl acetal → 5-[2-(3-Nitrophenylamino)-5-methyl-pyrimidin-4-yl]-4-cyclohexyl-2-methylsulfanyl-thiophene-3-carbonitrile

HRID 478191

Reaction equation

HRID 478191 reaction equation
[CH:1]1([C:7]2[C:8]([C:22]#[N:23])=[C:9]([S:20][CH3:21])[S:10][C:11]=2[C:12](=O)[C:13]([CH3:18])=[CH:14]N(C)C)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C(OC)OC)C.[N+:32]([C:35]1[CH:36]=[C:37]([NH:41][C:42]([NH2:44])=[NH:43])[CH:38]=[CH:39][CH:40]=1)([O-:34])=[O:33]>C1(C)C=CC=CC=1.CCOC(C)=O.CN(C=O)C>[N+:32]([C:35]1[CH:36]=[C:37]([NH:41][C:42]2[N:44]=[C:12]([C:11]3[S:10][C:9]([S:20][CH3:21])=[C:8]([C:22]#[N:23])[C:7]=3[CH:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)[C:13]([CH3:18])=[CH:14][N:43]=2)[CH:38]=[CH:39][CH:40]=1)([O-:34])=[O:33]

Participants

7

Reactant 3

HCID 78373Dimethylformamide dimethyl acetalHCID 695552744-Cyclohexyl-5-(3-dimethylamino-2-methyl-acryloyl)-2-methylsulfanyl-thiophene-3-carbonitrileHCID 178418758HCID 178418758, compound

Product 1

HCID 220190285-[2-(3-Nitrophenylamino)-5-methyl-pyrimidin-4-yl]-4-cyclohexyl-2-methylsulfanyl-thiophene-3-carbonitrileYield 42%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
90 °C

Procedure

To a solution of 4-cyclohexyl-5-(3-dimethylamino-2-methyl-acryloyl)-2-methylsulfanyl-thiophene-3-carbonitrile (0.5 g, 1.7 mmol) in toluene (3 ml) was added DMF-DMA and the reaction was heated at 90° C. overnight resulting in conversion to product as determined by TLC (40% EtOAc:hexanes). The crude product was combined with DMF (10 ml) and 3-Nitrophenylguanidine (0.5 g, 2.78 mmol) in a sealed tube and heated at 120° C. overnight resulting in conversion to product as determined by TLC (40% EtOAc:hexanes). The reaction was partitioned between EtOAc and water, the organics were dried over sodium sulfate then concentrated in vacuo. The crude product was purified by chromatography (silica gel, 10% EtOAC:hexanes) to afford 0.334 g (3.05 umol) of V-7 in 42% yield for 2 steps. 1H NMR (CDCl3) δ1.0-2.0 (m, 10H), 2.1 (s, 3H), 2.6(s, 3H), 7.4(m, 1H), 7.7 (d, 1H), 7.8 (d, 1H), 8.3 (s, 1H), 8.7 (s, 1H).

Workup

  1. customresulting in conversion to product
  2. temperatureheated at 120° C. overnight
  3. customresulting in conversion to product
  4. customThe reaction was partitioned between EtOAc and water
  5. dry with materialthe organics were dried over sodium sulfate
  6. concentrationthen concentrated in vacuo
  7. customThe crude product was purified by chromatography (silica gel, 10% EtOAC:hexanes)
  8. customto afford 0.334 g (3.05 umol) of V-7 in 42% yield for 2 steps

Sources & evidence

ORD record
ord-6b13f0f56ddc4635806ba795084de9b6
Source dataset
uspto-grants-2003_11
Patent number
US06642227B2

Linked notes

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