Diisopropylethylamine → {3-(3-Cyclopropyl-1,2,4-oxadiazol-5-yl)-5-[4-(difluoromethoxy)phenyl]piperidin-1-yl}(1-oxidothiomorpholin-4-yl)methanone

HRID 220062ノート

反応式

HRID 220062 の反応式
[F:1][CH:2]([F:28])[O:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:15][N:14]([C:16]([N:18]3[CH2:23][CH2:22][S:21](=[O:24])[CH2:20][CH2:19]3)=[O:17])[CH2:13][CH:12]([C:25](O)=[O:26])[CH2:11]2)=[CH:6][CH:5]=1.O[N:30]=[C:31]([CH:33]1[CH2:35][CH2:34]1)[NH2:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[CH:33]1([C:31]2[N:32]=[C:25]([CH:12]3[CH2:11][CH:10]([C:7]4[CH:8]=[CH:9][C:4]([O:3][CH:2]([F:1])[F:28])=[CH:5][CH:6]=4)[CH2:15][N:14]([C:16]([N:18]4[CH2:19][CH2:20][S:21](=[O:24])[CH2:22][CH2:23]4)=[O:17])[CH2:13]3)[O:26][N:30]=2)[CH2:35][CH2:34]1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2794666N'-HydroxycyclopropanecarboximidamideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 581165795-[4-(Difluoromethoxy)phenyl]-1-[(1-oxidothiomorpholin-4-yl)carbonyl]piperidine-3-carboxylic acid

生成物 1

HCID 59606592{3-(3-Cyclopropyl-1,2,4-oxadiazol-5-yl)-5-[4-(difluoromethoxy)phenyl]piperidin-1-yl}(1-oxidothiomorpholin-4-yl)methanone

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

200 mg (0.48 mmol) of the compound from Example 39A and 96 mg (0.96 mmol) of N′-hydroxycyclopropanecarboximidamide were initially charged in 1.8 ml of DMF and reacted with 274 mg (0.72 mmol) of HATU and 0.25 ml (186 mg, 1.44 mmol) of N,N-diisopropylethylamine. The reaction mixture was stirred at RT for 15 minutes and then partitioned between water and ethyl acetate. The organic phase was washed repeatedly with water, dried over sodium sulphate and concentrated under reduced pressure. The residue was dissolved in 2.0 ml of DMF and converted in a microwave at 180° C. for 2 minutes. The reaction mixture was purified by means of preparative HPLC. Yield: 25 mg (10% of theory)

後処理

  1. custompartitioned between water and ethyl acetate
  2. washThe organic phase was washed repeatedly with water
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in 2.0 ml of DMF
  6. waitconverted in a microwave at 180° C. for 2 minutes
  7. customThe reaction mixture was purified by means of preparative HPLC

出典と根拠

ORDレコード
ord-c6177610d67e4a7ba665c7776c583cb9
出典データセット
uspto-grants-2012_06
特許番号
US08202862B2

反応ノート

読み込み中…