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

HRID 2075360노트

반응식

HRID 2075360 반응식
[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

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
0 °C

실험 절차

(±)-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.

후처리

  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)

출처 및 근거

ORD 기록
ord-7bcbb004918f4f058f96fd1334ea8e84
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07919504B2

반응 노트

불러오는 중…