Thiophene-3-carboxylic acid → HCID 11949929, compound

HRID 2243656Notes

Reaction equation

HRID 2243656 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:29])=[C:6]([C:8]2[N:13]=[C:12]([S:14][CH3:15])[N:11]=[C:10]3[N:16]([C:21]4[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=4[F:28])[C:17](=[O:20])[NH:18][CH2:19][C:9]=23)[CH:7]=1.[S:30]1[CH:34]=[CH:33][C:32]([C:35](O)=[O:36])=[CH:31]1.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C>CN(C)C1C=CN=CC=1.C(Cl)(Cl)Cl>[F:27][C:26]1[CH:25]=[CH:24][CH:23]=[C:22]([F:28])[C:21]=1[N:16]1[C:10]2[N:11]=[C:12]([S:14][CH3:15])[N:13]=[C:8]([C:6]3[CH:7]=[C:2]([NH:1][C:35]([C:32]4[CH:33]=[CH:34][S:30][CH:31]=4)=[O:36])[CH:3]=[CH:4][C:5]=3[CH3:29])[C:9]=2[CH2:19][NH:18][C:17]1=[O:20]

Participants

7

Reactant 4

HCID 6918Thiophene-3-carboxylic acid2×HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 59208042HCID 59208042, compound

Product 1

HCID 11949929HCID 11949929, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6212ChloroformSolvent

Procedure

The compounds 5-(5-amino-2-methylphenyl)-1-(2,6-difluorophenyl)-7-(methylthio)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one (0.205 g, 0.5 mmol), 3-thiophenecarboxylic acid (0.0647 g, 0.5 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.107 g, 0.55 mmol), 4-(dimethylamino)pyridine (0.002 g, 0.016 mmol), and triethylamine (0.14 mL, 1 mmol), were dissolved in chloroform (10 mL) and stirred under argon at room temperature for 16 h. The reaction was not complete. An additional 3-thiophenecarboxylic acid (0.13 g, 1.0 mmol) and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.107 g, 0.55 mmol) were dded and heated to 40° C. for 17 h. The reaction mixture was partitioned between ethyl acetate and water. The organic phase was washed with water (3×), brine (1×), dried over anhydrous Na2SO4, filtered and evaporated. The crude product was flash chromatographed on silica gel (10 g) eluted with 0-5% MeOH/CH2Cl2 to give the title compound as a solid. LC-MS m/z 524 (M+H)+, 2.2 min (ret. time).

Workup

  1. temperatureheated to 40° C. for 17 h
  2. customThe reaction mixture was partitioned between ethyl acetate and water
  3. washThe organic phase was washed with water (3×), brine (1×)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customchromatographed on silica gel (10 g)
  8. washeluted with 0-5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-f177d6505ec04320bd85daa41a7013b4
Source dataset
uspto-grants-2010_03
Patent number
US07674789B2

Reaction notes

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