Triethylamine → N-{3-[8-(2,6-difluorophenyl)-2-(methylthio)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl]-4-methylphenyl}-2-thiophenecarboxamide

HRID 1806526Notes

Reaction equation

HRID 1806526 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:29])=[C:6]([C:8]2[C:9]3[CH:19]=[CH:18][C:17](=[O:20])[N:16]([C:21]4[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=4[F:28])[C:10]=3[N:11]=[C:12]([S:14][CH3:15])[N:13]=2)[CH:7]=1.CCN(CC)CC.[S:37]1[CH:41]=[CH:40][CH:39]=[C:38]1[C:42](Cl)=[O:43]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[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:42]([C:38]4[S:37][CH:41]=[CH:40][CH:39]=4)=[O:43])[CH:3]=[CH:4][C:5]=3[CH3:29])[C:9]=2[CH:19]=[CH:18][C:17]1=[O:20]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 789282-Thiophenecarbonyl chlorideHCID 592126794-(5-amino-2-methylphenyl)-8-(2,6-difluorophenyl)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one

Product 1

HCID 11948285N-{3-[8-(2,6-difluorophenyl)-2-(methylthio)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl]-4-methylphenyl}-2-thiophenecarboxamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(5-amino-2-methylphenyl)-8-(2,6-difluorophenyl)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one (411.0 mg, 1.0 mmol) in CH2Cl2 (10 mL) at 0° C. was added Et3N (200.0 mg, 2.0 mmol, 2.0 eq), DMAP (5.0 mg, 0.2 mmol, 0.2 eq) and 2-thiophenecarbonyl chloride (292.0 mg, 2.0 mmol, 2.0 eq). After addition the reaction mixture was stirred for about 14 h at ambient temperature. The mixture was concentrated and mixed with H2O (5.0 mL) and EtOAc (20.0 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (3×15 mL). The combined organic phases were washed with saturated aq. NaCl solution, dried over Na2SO4, filtered, and concentrated. Purification via a CombiFlash system (hexane:EtOAc; 4:1) then afforded the title compound: LC-MS m/z 521 (M+H)+, 2.57 min (ret time).

Workup

  1. additionAfter addition the reaction mixture
  2. concentrationThe mixture was concentrated
  3. additionmixed with H2O (5.0 mL) and EtOAc (20.0 mL)
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with EtOAc (3×15 mL)
  6. washThe combined organic phases were washed with saturated aq. NaCl solution
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification via a CombiFlash system (hexane:EtOAc; 4:1)

Sources & evidence

ORD record
ord-5005632e93c648aeb552a25bc25c9e53
Source dataset
uspto-grants-2013_01
Patent number
US08354416B2

Reaction notes

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