Aluminium lithium hydride → 1-(4-(2-(5-(3-Hydroxypropylthio)-3-phenoxypyridin-2-ylamino)thiazol-4-yl)piperidin-1-yl)ethanone

HRID 1809614Notes

Reaction equation

HRID 1809614 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([C:10]2[N:11]=[C:12]([NH:15][C:16]3[N:21]=[CH:20][C:19]([S:22][CH2:23][CH2:24][C:25](OC)=[O:26])=[CH:18][C:17]=3[O:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[S:13][CH:14]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[OH:26][CH2:25][CH2:24][CH2:23][S:22][C:19]1[CH:18]=[C:17]([O:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:16]([NH:15][C:12]2[S:13][CH:14]=[C:10]([CH:7]3[CH2:6][CH2:5][N:4]([C:1](=[O:3])[CH3:2])[CH2:9][CH2:8]3)[N:11]=2)=[N:21][CH:20]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 86631532Methyl 3-(6-(4-(1-acetylpiperidin-4-yl)thiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)propanoate

Product 1

HCID 592916191-(4-(2-(5-(3-Hydroxypropylthio)-3-phenoxypyridin-2-ylamino)thiazol-4-yl)piperidin-1-yl)ethanoneYield 21.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of methyl 3-(6-(4-(1-acetylpiperidin-4-yl)thiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)propanoate (100 mg, 0.195 mmol) in THF (10 mL) at 0° C. was treated dropwise with LiAlH4 (1M in THF, 195 μL, 0.195 mmol). Once the addition was completed the ice bath was removed and the mixture was stirred at ambient temperature for 30 minutes. The mixture was cooled to 0° C. and quenched with successive addition of water (0.2 mL), 2N NaOH (0.6 mL), and water (0.2 mL). The mixture was stirred at ambient temperature for 30 minutes and the resulting solids were removed by filtration, washing with additional THF. The filtrate was concentrated in vacuo and the residue was purified by reverse phase C-18 chromatography using a gradient of 20%-90% CH3CN/water to provide the title compound (20 mg, 0.0413 mmol, 21.2% yield) as a white solid. 1H NMR (DMSO-d6) δ 10.77 (brs, 1H), 8.11 (s, 1H), 7.42 (m, 2H), 7.86 (s, 1H), 7.18 (m, 1H), 7.06 (d, 2H), 6.66 (s, 1H), 4.49 (t, 1H), 4.42 (d, 1H), 3.85 (d, 1H), 3.44 (q, 2H), 3.12 (t, 1H), 2.88 (t, 2H), 2.80 (m, 1H), 2.62 (t, 1H), 2.00 (s, 3H), 1.92 (t, 2H), 1.66-1.59 (m, 2H), 1.57-1.41 (m, 2H).

Workup

  1. additionOnce the addition
  2. customwas removed
  3. temperatureThe mixture was cooled to 0° C.
  4. customquenched with successive addition of water (0.2 mL), 2N NaOH (0.6 mL), and water (0.2 mL)
  5. stirringThe mixture was stirred at ambient temperature for 30 minutes
  6. customthe resulting solids were removed by filtration
  7. washwashing with additional THF
  8. concentrationThe filtrate was concentrated in vacuo
  9. customthe residue was purified by reverse phase C-18 chromatography

Sources & evidence

ORD record
ord-2739dba22a444eb391e2493bff50c5b6
Source dataset
uspto-grants-2013_01
Patent number
US08362037B2

Reaction notes

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