Lithium borohydride → HCID 59291785, compound

HRID 1809627Notes

Reaction equation

HRID 1809627 reaction equation
[C:1]([N:4]1[CH:9]2[CH2:10][CH2:11][CH:5]1[CH2:6][CH:7]([C:12]1[N:16]=[C:15]([NH:17][C:18]3[N:23]=[CH:22][C:21]([S:24][CH2:25][C:26](OC)=[O:27])=[CH:20][C:19]=3[O:30][C:31]3[C:32]([CH3:37])=[N:33][CH:34]=[CH:35][CH:36]=3)[S:14][N:13]=1)[CH2:8]2)(=[O:3])[CH3:2].[Li+].[BH4-].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[OH:27][CH2:26][CH2:25][S:24][C:21]1[CH:20]=[C:19]([O:30][C:31]2[C:32]([CH3:37])=[N:33][CH:34]=[CH:35][CH:36]=2)[C:18]([NH:17][C:15]2[S:14][N:13]=[C:12]([CH:7]3[CH2:6][CH:5]4[N:4]([C:1](=[O:3])[CH3:2])[CH:9]([CH2:10][CH2:11]4)[CH2:8]3)[N:16]=2)=[N:23][CH:22]=1

Participants

5

Reactant 3

HCID 4148881Lithium borohydrideHCID 21226445Aluminium lithium hydrideHCID 67486976HCID 67486976, compound

Product 1

HCID 59291785HCID 59291785, compoundYield 26.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methyl 2-(6-(3-(8-acetyl-8-azabicyclo[3.2.1]octan-3-yl)-1,2,4-thiadiazol-5-ylamino)-5-(2-methylpyridin-3-yloxy)pyridin-3-ylthio)acetate (Prepared in Example 174, step d; 210 mg, 0.388 mmol) was dissolved in THF (4 mL) and LiBH4 (194 μL, 0.194 mmol) was added and stirred at ambient temperature for 30 minutes The reaction was cooled to 0° C. and LiAlH4 (194 μL, 0.194 mmol) was added and stirred for 20 minutes. The reaction was quenched with water and sodium sulfate, stirred for 10 minutes, filtered and concentrated. The residue was purified on silica gel (10% methanol in EtOAc) followed by reverse phase chromatography (5 to 95% ACN in water with 0.1% TFA) to afford 1-(3-(5-(5-(2-hydroxyethylthio)-3-(2-methylpyridin-3-yloxy)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)-8-azabicyclo[3.2.1]octan-8-yl)ethanone (52.5 mg, 0.102 mmol, 26.4% yield) as a solid after converting the salt to the free base. Mass spectrum (apci) m/z=513.2 (M+H).

Workup

  1. temperaturewas cooled to 0° C.
  2. stirringstirred for 20 minutes
  3. customThe reaction was quenched with water and sodium sulfate
  4. stirringstirred for 10 minutes
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified on silica gel (10% methanol in EtOAc)

Sources & evidence

ORD record
ord-fea678cb7bf44914bc746bba86c2e3b1
Source dataset
uspto-grants-2013_01
Patent number
US08362037B2

Reaction notes

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