Dimethylbarbituric acid → N-({5-[(4-heptanoylpiperidin-1-yl)sulfonyl]thien-2-yl}methyl)-3-methoxybenzamide

HRID 906645

Reaction equation

HRID 906645 reaction equation
C([N:4]([CH2:8][C:9]1[S:13][C:12]([S:14]([N:17]2[CH2:22][CH2:21][CH:20]([C:23](=[O:30])[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[CH2:19][CH2:18]2)(=[O:16])=[O:15])=[CH:11][CH:10]=1)CC=C)C=C.CN1C(=O)CC(=O)N(C)C1=O.CCN(C(C)C)C(C)C.[C:51](Cl)(=[O:60])[C:52]1[CH:57]=[CH:56][CH:55]=[C:54]([O:58][CH3:59])[CH:53]=1>C(Cl)Cl.C1COCC1.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:23]([CH:20]1[CH2:19][CH2:18][N:17]([S:14]([C:12]2[S:13][C:9]([CH2:8][NH:4][C:51](=[O:60])[C:52]3[CH:57]=[CH:56][CH:55]=[C:54]([O:58][CH3:59])[CH:53]=3)=[CH:10][CH:11]=2)(=[O:16])=[O:15])[CH2:22][CH2:21]1)(=[O:30])[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]

Participants

9

Reactant 4

HCID 69860Dimethylbarbituric acidHCID 74374m-Anisoyl chlorideHCID 81531DiisopropylethylamineHCID 674035001-[1-({5-[(Diallylamino)methyl]thien-2-yl}sulfonyl)piperidin-4-yl]heptan-1-one

Product 1

HCID 57443912N-({5-[(4-heptanoylpiperidin-1-yl)sulfonyl]thien-2-yl}methyl)-3-methoxybenzamideYield 50%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 327c (100 mg, 0.22 mmol), 1,3-Dimethylbarbituric acid (69 mg, 0.44 mmol) and Tetrakis(triphenylphosphine)palladium (12 mg, 0.01 mmol) were stirred in 3 mL CH2Cl2 overnight. The deprotection was followed by TLC. After complete cleavage of the protecting groups, the solvent was evaporated to dryness. The crude was taken up in THF, DIEA (76 ul, 0.33 mmol) was added, followed by the slow addition of 3-anisoylchloride (38 mg, 0.22 mmol) in THF. The reaction was stirred for 3 h, diluted with EtOAc and extracted with NaHCO3 and brine. The organic layers were dried over Na2SO4 and evaporated to dryness. The crude mixture was purified by flash chromatography on silica gel using cyclohexane/EtOAc 1:1 as eluent to obtain 30 mg (50%) of 327 as a colorless oil: H1 NMR (CDCl3) δ 7.40-7.10 (m, 3H), 6.95 (m, 2H), 6.45 (m, 1H), 4.70 (d, J=6.0 Hz, 2H), 3.74 (s, 3H), 3.58 (m, 2H), 2.40 (m, 2H), 2.27 (t, J=7.5 Hz, 2H), 2.19 (m, 1H), 1.77 (m, 2H), 1.64 (m, 2H), 1.13 (m, 8H), 0.74 (t, J=6.8 Hz, 3H), M/Z APCI: 506.3 (M+1).

Workup

  1. customAfter complete cleavage of the protecting groups, the solvent was evaporated to dryness
  2. extractionextracted with NaHCO3 and brine
  3. dry with materialThe organic layers were dried over Na2SO4
  4. customevaporated to dryness
  5. customThe crude mixture was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-343638b4a410443a8e80af95cd7a89c1
Source dataset
uspto-grants-2011_09
Patent number
US08012995B1

Linked notes

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