Sodium triacetoxyborohydride → 2-{1-[2-Chloro-9-methyl-6-((S)-3-methylmorpholin-4-yl)-9H-purin-8-ylmethyl]piperidin-4-yl}propan-2-ol

HRID 1945701Notes

Reaction equation

HRID 1945701 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH:12]=O)[N:8]2[CH3:11])=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]2[CH3:20])[N:3]=1.[NH:21]1[CH2:26][CH2:25][CH:24]([C:27]([OH:30])([CH3:29])[CH3:28])[CH2:23][CH2:22]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][N:21]3[CH2:26][CH2:25][CH:24]([C:27]([OH:30])([CH3:29])[CH3:28])[CH2:23][CH2:22]3)[N:8]2[CH3:11])=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]2[CH3:20])[N:3]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 52003212-(4-Piperidyl)-2-propanolHCID 596057572-Chloro-9-methyl-6-((S)-3-methylmorpholin-4-yl)-9H-purine-8-carbaldehyde

Product 1

HCID 596053212-{1-[2-Chloro-9-methyl-6-((S)-3-methylmorpholin-4-yl)-9H-purin-8-ylmethyl]piperidin-4-yl}propan-2-olYield 84%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 2-chloro-9-methyl-6-((S)-3-methylmorpholin-4-yl)-9H-purine-8-carbaldehyde (450 mg, 1.52 mmol), 2-piperidin-4-ylpropan-2-ol (239 mg, 1.67 mmol) and 4 Å powdered molecular sieves (450 mg) in DCE (10 mL) was stirred for 6 h before the addition of sodium triacetoxyborohydride (644 mg, 3.04 mmol). The resulting mixture was allowed to stir for 17 h then filtered through Celite®, washing with MeOH. The resulting filtrate was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH/DCM. The resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-4%) affording the title compound as a cream solid (538 mg, 84%). LCMS (method H): RT 2.02 min [M+H]+ 423.3

Workup

  1. filtrationthen filtered through Celite®
  2. washwashing with MeOH
  3. washwas washed with MeOH
  4. washthe product eluted with 2M NH3/MeOH/DCM
  5. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-4%)

Sources & evidence

ORD record
ord-4bd3f0b425164014b0367547bb6b86b1
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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