Triethylamine → 6-(4-fluorophenyl)-3-{2-[4-(1-pyrrolidin-1-ylethyl)phenyl]ethyl}thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione

HRID 1668399Notes

Reaction equation

HRID 1668399 reaction equation
[NH2:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[S:4][C:3]=1[C:14]([NH:16][CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([CH:25]([N:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)[CH3:26])=[CH:21][CH:20]=1)=[O:15].C(N(CC)CC)C.Cl[C:40](Cl)([O:42]C(=O)OC(Cl)(Cl)Cl)Cl.N1CCCC1>ClCCCl.C(OCC)(=O)C>[F:13][C:10]1[CH:11]=[CH:12][C:7]([C:5]2[S:4][C:3]3[C:14](=[O:15])[N:16]([CH2:17][CH2:18][C:19]4[CH:24]=[CH:23][C:22]([CH:25]([N:27]5[CH2:31][CH2:30][CH2:29][CH2:28]5)[CH3:26])=[CH:21][CH:20]=4)[C:40](=[O:42])[NH:1][C:2]=3[CH:6]=2)=[CH:8][CH:9]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 31268PyrrolidineHCID 94429TriphosgeneHCID 673594643-amino-5-(4-fluorophenyl)-N-{2-[4-(1-pyrrolidin-1-ylethyl)phenyl]ethyl}thiophene-2-carboxamide

Product 1

HCID 592398686-(4-fluorophenyl)-3-{2-[4-(1-pyrrolidin-1-ylethyl)phenyl]ethyl}thieno[3,2-d]pyrimidine-2,4(1H,3H)-dioneYield 19.2%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

The obtained 3-amino-5-(4-fluorophenyl)-N-{2-[4-(1-pyrrolidin-1-ylethyl)phenyl]ethyl}thiophene-2-carboxamide (0.15 g) was suspended in 1,2-dichloroethane (5 ml), and triethylamine (0.067 ml) and triphosgene (0.080 g) were successively added with stirring. After 3 hr, pyrrolidine (0.8 ml) was added, and the reaction mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (hexane:ethyl acetate=9:1 (volume ratio)→1:2 (volume ratio)) using NH-silica gel, and further recrystallized from ethyl acetate to give the title compound (0.024 g) as pale-yellow crystals.

Workup

  1. stirringthe reaction mixture was stirred overnight at room temperature
  2. washwashed with water and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by column chromatography (hexane
  6. customfurther recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-3ef1295ccde44e2a85f5f453d428fbc3
Source dataset
uspto-grants-2011_08
Patent number
US07989445B2

Reaction notes

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