Aluminium lithium hydride → HCID 57750341, compound

HRID 423061Notes

Reaction equation

HRID 423061 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[C:7]([O:11][C:12]([NH:14][C:15]1([C:30]([NH:32][C@@H:33]([C:39]2[CH:44]=[CH:43][C:42]([Cl:45])=[CH:41][CH:40]=2)[CH2:34][C:35](OC)=[O:36])=[O:31])[CH2:20][CH2:19][N:18]([C:21]2[C:22]3[CH:29]=[CH:28][NH:27][C:23]=3[N:24]=[CH:25][N:26]=2)[CH2:17][CH2:16]1)=[O:13])([CH3:10])([CH3:9])[CH3:8]>C1COCC1>[Cl:45][C:42]1[CH:41]=[CH:40][C:39]([C@H:33]([NH:32][C:30]([C:15]2([NH:14][C:12](=[O:13])[O:11][C:7]([CH3:9])([CH3:8])[CH3:10])[CH2:16][CH2:17][N:18]([C:21]3[C:22]4[CH:29]=[CH:28][NH:27][C:23]=4[N:24]=[CH:25][N:26]=3)[CH2:19][CH2:20]2)=[O:31])[CH2:34][CH2:35][OH:36])=[CH:44][CH:43]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 57750401HCID 57750401, compound2×

Product 1

HCID 57750341HCID 57750341, compoundYield 21.63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

LiAlH4 (1.398 mL, 1.40 mmol) was added dropwise to (R)-methyl 3-(4-(tert-butoxycarbonylamino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamido)-3-(4-chlorophenyl)propanoate (Intermediate 41) (779 mg, 1.40 mmol) in THF (40 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 20° C. for 3 hours. The reaction mixture was quenched with water (1 mL) and neutralised with 2M HCl. The reaction mixture was evaporated to dryness and redissolved in DCM (100 mL) and washed with water (100 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM. The pure fractions were combined and evaporated to give (R)-tert-butyl 4-(1-(4-chlorophenyl)-3-hydroxypropylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate (160 mg, 21.63%) as a solid.

Workup

  1. customThe reaction mixture was quenched with water (1 mL)
  2. customThe reaction mixture was evaporated to dryness
  3. dissolutionredissolved in DCM (100 mL)
  4. washwashed with water (100 mL)
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customto afford crude product
  9. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM
  10. customevaporated

Sources & evidence

ORD record
ord-2591d3d7ef94450fbba8355ffe4f789f
Source dataset
uspto-grants-2012_01
Patent number
US08101623B2

Reaction notes

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