Diisopropylethylamine → N-methyl-3-{1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-N-((R)-1-phenyl-ethyl)-benzamide

HRID 385296

反応式

HRID 385296 の反応式
[CH3:1][C:2]1[N:6]([CH2:7][C:8]([N:10]2[CH2:15][CH2:14][CH:13]([C:16]3[CH:17]=[C:18]([CH:22]=[CH:23][CH:24]=3)[C:19](O)=[O:20])[CH2:12][CH2:11]2)=[O:9])[N:5]=[C:4]([C:25]([F:28])([F:27])[F:26])[CH:3]=1.C(N(C(C)C)CC)(C)C.C[NH3+].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.[CH3:71][NH:72][C@@H:73]([C:75]1[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=1)[CH3:74]>CN(C=O)C>[CH3:71][N:72]([C@@H:73]([C:75]1[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=1)[CH3:74])[C:19](=[O:20])[C:18]1[CH:22]=[CH:23][CH:24]=[C:16]([CH:13]2[CH2:12][CH2:11][N:10]([C:8](=[O:9])[CH2:7][N:6]3[C:2]([CH3:1])=[CH:3][C:4]([C:25]([F:28])([F:27])[F:26])=[N:5]3)[CH2:15][CH2:14]2)[CH:17]=1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2060888(R)-(+)-N-Methyl-1-phenylethylamineHCID 669733373-{1-[2-(5-Methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]piperidin-4-yl}-benzoic acidHCID 866211442-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate Methanaminium

生成物 1

HCID 66973078N-methyl-3-{1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-N-((R)-1-phenyl-ethyl)-benzamide収率 41.5%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 3-{1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-benzoic acid (320 mg, 0.80 mmol) in DMF (8 mL) was added diisopropylethylamine (1.01 mL, 4.85 mmol), followed by 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate methanaminium (0.41 g, 0.89 mmol) at RT. After stirring for 15 min. at RT, Methyl-((R)-1-phenyl-ethyl)-amine (0.132 g, 0.80 mmol) was added to the reaction mixture. After stirring for 2 h at RT, solvent was evaporated and the resulting brown oil was dissolved in ethylacetate (20 mL), washed with aq. sat. sodium bicarbonate solution (30 mL) and the aqueous phase was re-extracted with ethylacetate (20 mL). The combined organic layers were washed with 1M HCl solution (50 mL) and brine (50 mL), dried over sodium sulfate, filtered, and evaporated under reduce pressure. The crude mixture was purified by column chromatography on silica gel (ethylacetate/cyclohexane 1:1 to 8:2) to give N-methyl-3-{1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-N—((R)-1-phenyl-ethyl)-benzamide (170 mg, 41%). 1H-NMR (400 MHz, d6-DMSO): δ=1.55 (d, 3H), 1.62-1.71 (m, 1H), 1.82-1.89 (m, 2H), 1.99 (s, 3H), 2.22 (s, 3H), 2.54-2.73 (m, 3H), 2.81-2.90 (m, 1H), 3.12-3.21 (m, 1H), 3.99-4.04 (m, 1H), 4.46-4.52 (m, 1H), 5.19-5.38 (m, 2H), 6.50 (s, 1H), 7.12-7.41 (m, 9H). MS: m/z=513 (M+1)

後処理

  1. stirringAfter stirring for 2 h at RT
  2. customsolvent was evaporated
  3. dissolutionthe resulting brown oil was dissolved in ethylacetate (20 mL)
  4. washwashed with aq. sat. sodium bicarbonate solution (30 mL)
  5. extractionthe aqueous phase was re-extracted with ethylacetate (20 mL)
  6. washThe combined organic layers were washed with 1M HCl solution (50 mL) and brine (50 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customThe crude mixture was purified by column chromatography on silica gel (ethylacetate/cyclohexane 1:1 to 8:2)

出典と根拠

ORDレコード
ord-afb6fd412c4e42238497afe85655f0e8
出典データセット
uspto-grants-2013_02
特許番号
US08367844B2

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