Potassium Sodium Tartrate → (+/-)-1-(5-(Isoquinolin-6-yl)-1,3,4-thiadiazol-2-ylamino)-3-phenylpropan-2-ol

HRID 2075360ノート

反応式

HRID 2075360 の反応式
[Si]([O:8][CH:9]([CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:10]([NH:12][C:13]1[S:14][C:15]([C:18]2[CH:19]=[C:20]3[C:25](=[CH:26][CH:27]=2)[CH:24]=[N:23][CH:22]=[CH:21]3)=[N:16][N:17]=1)=O)(C(C)(C)C)(C)C.[H-].[Al+3].[Li+].[H-].[H-].[H-].[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C1COCC1.CCOCC>[CH:24]1[C:25]2[C:20](=[CH:19][C:18]([C:15]3[S:14][C:13]([NH:12][CH2:10][CH:9]([OH:8])[CH2:28][C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)=[N:17][N:16]=3)=[CH:27][CH:26]=2)[CH:21]=[CH:22][N:23]=1

参加物

6

反応物 3

HCID 9357Potassium Sodium TartrateHCID 21226445Aluminium lithium hydrideHCID 67089607(+/-)-2-(tert-butyldimethylsilyloxy)-N-(5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-yl)-3-phenylpropanamide

生成物 1

HCID 57991868(+/-)-1-(5-(Isoquinolin-6-yl)-1,3,4-thiadiazol-2-ylamino)-3-phenylpropan-2-ol収率 2%

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

(±)-2-(tert-Butyldimethylsilyloxy)-N-(5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-yl)-3-phenylpropanamide (0.44 g, 0.9 mmol) was taken up in 9 mL of THF and chilled to 0° C. Lithium aluminum hydride (4 mL, 1.0 M in THF) was added. After 1 hour, the mixture was poured into 50 mL of ½ saturated aqueous Rochelle's salt and diluted with 25 mL of ether. The mixture was stirred for 1 hour. The mixture was partitioned in a separatory funnel, and the aqueous portion was extracted twice with 50 mL of EtOAc. The combined organic extracts were washed with 50 mL of brine and dried over MgSO4. Filtration and concentration under reduced pressure, followed by purification by flash chromatography on silica gel (eluting with a gradient of 2% to 10% MeOH in DCM) afforded (±)-1-(5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-ylamino)-3-phenylpropan-2-ol (0.005 g, 2%) as a yellow oil. LCMS (M+H) 363 calc. for C20H19N4OS 363.1. 1H NMR (400 MHz, CD3OD): ppm 9.27 (s, 1H), 8.50 (d, J=5.2 Hz, 1H), 8.24 (s, 1H), 8.20 (d, J=1.5 Hz, 2H), 7.90 (d, J=5.8 Hz, 1H) 7.33-7.29 (m, 5H), 7.26-7.22 (m, 1H), 4.14-4.10 (m, 1H), 3.60 (dd, J=3.9 Hz, 13.5 Hz, 1H), 3.40 (dd, J=7.5 Hz, 13.5 Hz, 1H), 2.91 (dd, J=5.4 Hz, 13.7 Hz, 1H), 2.82 (dd, J=7.6 Hz, 13.7 Hz, 1H). 1H not detected.

後処理

  1. customThe mixture was partitioned in a separatory funnel
  2. extractionthe aqueous portion was extracted twice with 50 mL of EtOAc
  3. washThe combined organic extracts were washed with 50 mL of brine
  4. dry with materialdried over MgSO4
  5. filtrationFiltration and concentration under reduced pressure
  6. customfollowed by purification by flash chromatography on silica gel (
  7. washeluting with a gradient of 2% to 10% MeOH in DCM)

出典と根拠

ORDレコード
ord-7bcbb004918f4f058f96fd1334ea8e84
出典データセット
uspto-grants-2011_04
特許番号
US07919504B2

反応ノート

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