Dimethylformamide → (S)-6-(2-Hydroxy-2-methyl-propyl)-3-{(S)-1-[4-(1-methyl-2-oxo-1,2-dihydro-pyridin-4-ylethynyl)-phenyl]ethyl}-6-phenyl-[1,3]oxazinan-2-one

HRID 333909

反応式

HRID 333909 の反応式
CCN(CC)CC.Br[C:9]1[CH:14]=[CH:13][N:12]([CH3:15])[C:11](=[O:16])[CH:10]=1.[C:17]([C:19]1[CH:24]=[CH:23][C:22]([C@@H:25]([N:27]2[CH2:32][CH2:31][C@:30]([CH2:39][C:40]([OH:43])([CH3:42])[CH3:41])([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[O:29][C:28]2=[O:44])[CH3:26])=[CH:21][CH:20]=1)#[CH:18].CN(C)C=O>[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[OH:43][C:40]([CH3:41])([CH3:42])[CH2:39][C@@:30]1([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[O:29][C:28](=[O:44])[N:27]([C@H:25]([C:22]2[CH:21]=[CH:20][C:19]([C:17]#[C:18][C:9]3[CH:14]=[CH:13][N:12]([CH3:15])[C:11](=[O:16])[CH:10]=3)=[CH:24][CH:23]=2)[CH3:26])[CH2:32][CH2:31]1

参加物

8

反応物 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 221323964-Bromo-1-methylpyridin-2(1H)-oneHCID 86670541(S)-3-((S)-1-(4-ethynylphenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one

生成物 1

HCID 66869817(S)-6-(2-Hydroxy-2-methyl-propyl)-3-{(S)-1-[4-(1-methyl-2-oxo-1,2-dihydro-pyridin-4-ylethynyl)-phenyl]ethyl}-6-phenyl-[1,3]oxazinan-2-one

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 962Water溶媒

反応条件

温度
100 °C

実験手順

CuI (68 mg), Pd(PPh3)2Cl2 (125 mg), and NEt3 (0.82 mL) were added successively to a flask charged with a stir bar, 4-bromo-1-methyl-1H-pyridin-2-one (0.38 g), 3-[(S)-1-(4-ethynyl-phenyl)-ethyl]-(S)-6-(2-hydroxy-2-methyl-propyl)-6-phenyl-[1,3]oxazinan-2-one (0.61 g), and N,N-dimethylformamide (3 mL) and kept at room temperature under argon atmosphere. The resulting mixture was heated to 100° C. and stirred at this temperature for 4 h. After cooling the mixture to ambient temperature, water was added and the resulting mixture was extracted with ethyl acetate. The combined organic extracts were washed with water and brine and dried (MgSO4). The solvent was evaporated and the residue was chromatographed on silica gel twice (first chromatography: ethyl acetate/methanol 1:0->4:1; second chromatography: dichloromethane/methanol 19:1->9:1) to afford the title compound as an oil which crystallized from ethyl acetate. Yield: 0.27 g (34% of theory); LC-MS (Method 1): tR=3.41 min; Mass spectrum (ESI+): m/z=485 [M+H]+.

後処理

  1. additioncharged with a stir bar
  2. customkept at room temperature under argon atmosphere
  3. temperatureAfter cooling the mixture to ambient temperature
  4. extractionthe resulting mixture was extracted with ethyl acetate
  5. washThe combined organic extracts were washed with water and brine
  6. dry with materialdried (MgSO4)
  7. customThe solvent was evaporated
  8. customthe residue was chromatographed on silica gel twice (first chromatography: ethyl acetate/methanol 1:0->4:1; second chromatography: dichloromethane/methanol 19:1->9:1)

出典と根拠

ORDレコード
ord-8737c493692d403fb7d6f6ec83060ed2
出典データセット
uspto-grants-2014_11
特許番号
US08883778B2

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