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

HRID 2075360Notes

Reaction equation

HRID 2075360 reaction equation
[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

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

(±)-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.

Workup

  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)

Sources & evidence

ORD record
ord-7bcbb004918f4f058f96fd1334ea8e84
Source dataset
uspto-grants-2011_04
Patent number
US07919504B2

Reaction notes

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