Aluminium lithium hydride → HCID 57463211, compound

HRID 1783845Notes

Reaction equation

HRID 1783845 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][CH2:14][C@@H:13]([NH:17][C:18]3[N:23]=[C:22]([C:24]4[N:31]5[C:27]([S:28][CH:29]=[CH:30]5)=[N:26][C:25]=4[C:32]4[CH:33]=[C:34]([CH:37]=[CH:38][CH:39]=4)[CH:35]=[O:36])[CH:21]=[CH:20][N:19]=3)[CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][CH2:14][C@@H:13]([NH:17][C:18]3[N:23]=[C:22]([C:24]4[N:31]5[C:27]([S:28][CH:29]=[CH:30]5)=[N:26][C:25]=4[C:32]4[CH:33]=[C:34]([CH2:35][OH:36])[CH:37]=[CH:38][CH:39]=4)[CH:21]=[CH:20][N:19]=3)[CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 57463206HCID 57463206, compound

Product 1

HCID 57463211HCID 57463211, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture 3-{5-[2-({(3R)-1-[(4-chlorophenyl)sulfonyl]piperidin-3-yl}amino)pyrimidin-4-yl]imidazo [2,1-b][1,3]thiazol-6-yl}benzaldehyde (0.20 g, 0.346 mmol) in anhydrous tetrahydrofuran (THF) (5.0 mL) at room temperature was added a solution of lithium aluminum hydride (LAH) (2.0 M in THF) (0.346 mL, 0.692 mmol). The mixture was stirred for one hour, then quenched with methanol (1.0 mL), diluted with dichloromethane (50 mL) and 30 mL of water. Organic layer was separated and the water layer was extracted with dichloromethane (50 mL×2). Organic layer was combined, dried over sodium sulfate and concentrated. Product was purified by flash chromatography on silica gel (methanol:dichloromethane:ethylacetate=0.5:7:2) to afford 0.142 g (71%) of the title compound as an off-white solid. M.p.=150-155° C. 400 MHz 1H NMR (DMSO-d6 at 60° C.) δ: 8.75 (bs, 1H), 8.12 (d, J=5.6 Hz, 1H), 7.77-7.74 (m, 2H), 7.67-7.65 (m, 2H), 7.56 (s, 1H), 7.44-7.36 (m, 4H), 7.11 (d, J=7.2 Hz, 1H), 6.39 (d, J=5.6 Hz, 1H), 5.07 (t, J=5.6 Hz, 1H), 4.55 (d, J=6.0 Hz, 2H), 3.29 (br. s, 1H), 3.73 (d, J=7.2 Hz, 1H), 3.48 (d, J=11.2 Hz, 1H), 2.5-2.43 (m, 1H), 2.35 (t, J=10.0 Hz, 1H), 1.91-1.82 (m, 2H), 1.60-1.57 (m, 1H), 1.40-1.32 (m, 1H). LCMS: 581 [M+H].

Workup

  1. customquenched with methanol (1.0 mL)
  2. additiondiluted with dichloromethane (50 mL) and 30 mL of water
  3. customOrganic layer was separated
  4. extractionthe water layer was extracted with dichloromethane (50 mL×2)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customProduct was purified by flash chromatography on silica gel (methanol:dichloromethane:ethylacetate=0.5:7:2)

Sources & evidence

ORD record
ord-cc1c0bcfdd8d4f3bba5acc4f84a0f39d
Source dataset
uspto-grants-2009_03
Patent number
US07501430B2

Reaction notes

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