Diisopropylethylamine → 3,5-dichloro-N-[(2S)-2-(4-fluorophenyl)-4-(3-morpholin-4-ylazetidin-1-yl)butyl]-N-methylbenzamide

HRID 749413ノート

反応式

HRID 749413 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([CH2:28][CH2:29]N2CC(N3CCC(O)CC3)C2)[CH2:9][N:10]([CH3:27])[C:11](=[O:26])[C:12]2[CH:17]=[C:16](C(F)(F)F)[CH:15]=[C:14](C(F)(F)F)[CH:13]=2)=[CH:4][CH:3]=1.[ClH:41].[ClH:42].[NH:43]1[CH2:46][CH:45]([N:47]2[CH2:52][CH2:51][O:50][CH2:49][CH2:48]2)[CH2:44]1.CCN(C(C)C)C(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.C(O)(=O)C>[Cl:41][C:14]1[CH:13]=[C:12]([CH:17]=[C:16]([Cl:42])[CH:15]=1)[C:11]([N:10]([CH2:9][C@H:8]([C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[CH2:28][CH2:29][N:43]1[CH2:46][CH:45]([N:47]2[CH2:52][CH2:51][O:50][CH2:49][CH2:48]2)[CH2:44]1)[CH3:27])=[O:26]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 11455933N-{(2S)-2-(4-fluorophenyl)-4-[3-(4-hydroxypiperidin-1-yl)azetidin-1-yl]butyl}-N-methyl-3,5-bis(trifluoromethyl)benzamideHCID 220613264-(Azetidin-3-yl)morpholine dihydrochloride

生成物 1

HCID 112604303,5-dichloro-N-[(2S)-2-(4-fluorophenyl)-4-(3-morpholin-4-ylazetidin-1-yl)butyl]-N-methylbenzamide収率 63%

試薬・触媒・溶媒 2

HCID 176Acetic Acid触媒HCID 6344Dichloromethane溶媒

実験手順

3,5-Dichloro-N-[(2S)-2-(4-fluorophenyl)-4-oxobutyl]-N-methylbenzamide (see Method 21; 146 mg, 0.40 mmol) was dissolved in CH2Cl2 (8 mL) and to the resultant solution were added 4-azetidin-3-ylmorpholine dihydrochloride (see WO 00/63168; 62 mg, 0.44 mmol) and DIPEA (179 mg, 1.39 mmol) together with 5 drops of acetic acid. The mixture was stirred for 25 minutes and then sodium triacetoxyborohydride (118 mg, 0.55 mmol) was added. The mixture was stirred at room temperature overnight. The solvent was evaporated and the residue was partitioned between ethyl acetate and saturated NaHCO3 aq. The phases were separated and the aqueous solution was extracted with ethyl acetate. The combined organic solutions were dried over MgSO4 and the solvent was removed by evaporation. The residue was chromatographed on silica gel using a mixture of methanol and CH2Cl2 as eluent (gradient 0 to 20% methanol). There was obtained 124 mg (63%) of the title compound as an oil. 1H NMR (500 MHz, CDCl3): 1.4-1.8 (cm, 2H), 2.2-3.8 (cm, 21H), 6.7 (s, 1H), 6.8-7.2 (m, 5H), 7.3 (s, 1H); LCMS: m/z 494 (M+1)+.

後処理

  1. stirringThe mixture was stirred at room temperature overnight
  2. customThe solvent was evaporated
  3. customthe residue was partitioned between ethyl acetate and saturated NaHCO3 aq. The phases
  4. customwere separated
  5. extractionthe aqueous solution was extracted with ethyl acetate
  6. dry with materialThe combined organic solutions were dried over MgSO4
  7. customthe solvent was removed by evaporation
  8. customThe residue was chromatographed on silica gel using
  9. additiona mixture of methanol and CH2Cl2 as eluent (gradient 0 to 20% methanol)

出典と根拠

ORDレコード
ord-b6d39ddb8f4a4ca2847adcbddaa04e48
出典データセット
uspto-grants-2008_07
特許番号
US07402581B2

反応ノート

読み込み中…