N'-((2R,3S)-2-(3-Chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)-4-(1H-pyrazol-1-yl)benzohydrazide → 4-((1R,2S)-1-(5-(4-(1H-pyrazol-1-yl)phenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxypropylamino)-2-chloro-3-methylbenzonitrile

HRID 470835

反応式

HRID 470835 の反応式
[Cl:1][C:2]1[C:3]([CH3:32])=[C:4]([NH:10][C@H:11]([C@@H:29]([OH:31])[CH3:30])[C:12]([NH:14][NH:15][C:16](=O)[C:17]2[CH:22]=[CH:21][C:20]([N:23]3[CH:27]=[CH:26][CH:25]=[N:24]3)=[CH:19][CH:18]=2)=[O:13])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].C(NP1(N(CC)CC)N(C)CCCN1C)(C)(C)C>C1COCC1>[N:23]1([C:20]2[CH:19]=[CH:18][C:17]([C:16]3[O:13][C:12]([C@H:11]([NH:10][C:4]4[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[C:2]([Cl:1])[C:3]=4[CH3:32])[C@@H:29]([OH:31])[CH3:30])=[N:14][N:15]=3)=[CH:22][CH:21]=2)[CH:27]=[CH:26][CH:25]=[N:24]1

参加物

4

反応物 2

HCID 67005755N'-((2R,3S)-2-(3-Chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)-4-(1H-pyrazol-1-yl)benzohydrazideHCID 178464497HCID 178464497、化合物

生成物 1

HCID 441995864-((1R,2S)-1-(5-(4-(1H-pyrazol-1-yl)phenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxypropylamino)-2-chloro-3-methylbenzonitrile収率 15.3%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of N′-((2R,3S)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)-4-(1H-pyrazol-1-yl)benzohydrazide (164 mg, 0.36 mmol) in anhydrous THF (12 mL) at room temperature was added 2-tert-butylamino-2-diethylamino-1,3-dimethyl perhydro-1,3,2-diazaphosphorine on polystyrene (2.2 mmol base/1) (495 mg, 1.09 mmol) followed by p-TSCl (83 mg, 0.44 mmol) and the mixture was stirred for 70 mm. The mixture was filtered under suction and the residue washed with acetone (2×50 mL) followed by MeOH (2×50 mL). The filtrate was concentrated under reduced pressure to provide a off white solid, which was purified by flash chromatography over silica gel (25-50% EtOAc in hexanes) to provided 4-((1R,2S)-1-(5-(4-(1H-pyrazol-1-yl)phenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxypropylamino)-2-chloro-3-methylbenzonitrile as a yellow oil (24 mg, 15%): 1H NMR (400 MHz, acetone-d6, δ in ppm) 8.46 (d, J=2.5 Hz, 1H), 8.11 (dm, J=9.2 Hz, 2H), 8.06 (dm, J=9.0 Hz, 2H), 7.77 (d. J=1.8 Hz, 1H), 7.50 (d, J=8.8 Hz, 1H), 6.88 (d, J=8.8 Hz, 1H), 6.57 (dd, J=1.8, 2.5 Hz, 1H), 5.70 (d, J=8.6 Hz, 1H), 5.12 (dd, J=3.5, 8.6 Hz, 1H), 4.86 (br s, 1H), 4.69-4.60 (m, 1H), 2.41 (5, 3H), 1.42 (d, J=6.5 Hz, 3H).

後処理

  1. filtrationThe mixture was filtered under suction
  2. washthe residue washed with acetone (2×50 mL)
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customto provide a off white solid, which
  5. customwas purified by flash chromatography over silica gel (25-50% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-4cd4a3fac1174ec0bbec0ee9d90ece4f
出典データセット
uspto-grants-2014_01
特許番号
US08629167B2

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