Diisopropylethylamine → (3-(4-((3-(Difluoromethyl)azetidin-1-yl)methyl)phenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone

HRID 1035233ノート

反応式

HRID 1035233 の反応式
[C:1]1([C:7]2[O:11][C:10]([C:12]([N:14]3[CH2:17][CH:16]([O:18][C:19]4[CH:26]=[CH:25][C:22]([CH:23]=O)=[CH:21][CH:20]=4)[CH2:15]3)=[O:13])=[N:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[F:28][CH:29]([F:34])[CH:30]1[CH2:33][NH:32][CH2:31]1.CCN(C(C)C)C(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[F:28][CH:29]([F:34])[CH:30]1[CH2:33][N:32]([CH2:23][C:22]2[CH:21]=[CH:20][C:19]([O:18][CH:16]3[CH2:17][N:14]([C:12]([C:10]4[O:11][C:7]([C:1]5[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=5)=[N:8][N:9]=4)=[O:13])[CH2:15]3)=[CH:26][CH:25]=2)[CH2:31]1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 58043115HCID 58043115、化合物HCID 666534863-(Difluoromethyl)azetidine hydrochloride

生成物 1

HCID 56598797(3-(4-((3-(Difluoromethyl)azetidin-1-yl)methyl)phenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone収率 19%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a suspension of 68A (0.20 g, 0.57 mmol) in DCM (3 mL) was added 68C (0.25 g, 1.72 mmol) followed by DIPEA (0.30 mL, 1.72 mmol). Sodium triacetoxyborohydride (0.24 g, 1.15 mmol) was added. The mixture was stirred at RT for 5 h and then diluted with DCM. The solution was washed with an aqueous solution of NaHCO3 and then filtered through a phase separator. The solvent was removed by evaporation. The product was purified on a silica gel column using 1-4% methanol in DCM where the methanol contained 2M ammonia. The product was triturated from ether and after drying in the hood there was obtained 47 mg (19%) of 68 as a solid. 1H NMR (500 MHz, CDCl3): δ 2.86 (m, 1H), 3.19 (m, 2H), 3.36 (m, 2H), 3.55 (s, 2H), 4.34 (dd, 1H), 4.64 (dd, 1H), 4.78 (dd, 1H), 5.07 (m, 1H), 5.11 (m, 1H), 5.99 (t, 1H), 6.74 (d, 2H), 7.22 (d, 2H), 7.54 (t, 2H), 7.59 (t, 1H), 8.16 (d, 2H), MS (APCI+) m/z 441 [M+H]+, LC purity: 90%. A sample of (3-(4-((3-(difluoromethyl)azetidin-1-yl)methyl)phenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone was recrystallised from DCM/Et2O had m. p. 147° C. (purity 99%).

後処理

  1. washThe solution was washed with an aqueous solution of NaHCO3
  2. filtrationfiltered through a phase separator
  3. customThe solvent was removed by evaporation
  4. customThe product was purified on a silica gel column
  5. customThe product was triturated from ether
  6. customafter drying in the hood there

出典と根拠

ORDレコード
ord-161a1eb333d442318f3ad55e00aec34e
出典データセット
uspto-grants-2013_10
特許番号
US08546375B2

反応ノート

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