Sodium triacetoxyborohydride → 7-[2-(2-Chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)ethyl]-7-azaspiro[3.5]nonan-2-ol

HRID 1945644Notes

Reaction equation

HRID 1945644 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][CH:13]=O)[N:8]2[CH3:11])=[C:4]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[N:3]=1.[CH2:21]1[C:24]2([CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)[CH2:23][CH:22]1[OH:30].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][CH2:13][N:27]3[CH2:28][CH2:29][C:24]4([CH2:21][CH:22]([OH:30])[CH2:23]4)[CH2:25][CH2:26]3)[N:8]2[CH3:11])=[C:4]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[N:3]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 111710267-Azaspiro[3.5]nonan-2-olHCID 59605819(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)acetaldehyde

Product 1

HCID 596053687-[2-(2-Chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)ethyl]-7-azaspiro[3.5]nonan-2-olYield 69.5%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of (2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)acetaldehyde (157 mg, 0.53 mmol) in DCE (10 mL) was added 7-azaspiro[3.5]nonan-2-ol (109 mg, 0.77 mmol) and powdered 4 Å molecular sieves. The reaction mixture was stirred at room temperature for 4 h, sodium triacetoxyborohydride (225 mg, 1.06 mmol) was added and the resulting mixture stirred for a further 16 h. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH then the desired product eluted with 2 M NH3 in MeOH. The resulting residue was purified by column chromatography (Si—PCC, 0-10% 2 M NH3/MeOH in DCM) to give the title compound as a colourless oil (155 mg, 69%). LCMS (Method H): RT=2.41 min, [M+H]+ 421.5

Workup

  1. stirringthe resulting mixture stirred for a further 16 h
  2. washwashed with MeOH
  3. washthe desired product eluted with 2 M NH3 in MeOH
  4. customThe resulting residue was purified by column chromatography (Si—PCC, 0-10% 2 M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-8dfa1614cc2f44fb94203e9075d3260c
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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