Hydrochloric Acid → 2-Chloro-8-[2-(3,3-dimethylmorpholin-4-yl)ethyl]-9-methyl-6-morpholin-4-yl-9H-purine

HRID 1945649Notes

Reaction equation

HRID 1945649 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.[CH3:21][C:22]1([CH3:28])[CH2:27][O:26][CH2:25][CH2:24][NH:23]1.Cl.C(N(CC)CC)C.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:23]3[CH2:24][CH2:25][O:26][CH2:27][C:22]3([CH3:28])[CH3:21])[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

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 145518493,3-DimethylmorpholineHCID 59605819(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)acetaldehyde

Product 1

HCID 596061282-Chloro-8-[2-(3,3-dimethylmorpholin-4-yl)ethyl]-9-methyl-6-morpholin-4-yl-9H-purineYield 28%

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 (119 mg, 0.40 mmol) in DCE (10 mL) was added 3,3-dimethylmorpholine.HCl (61 mg, 0.40 mmol), triethylamine (0.06 mL, 0.40 mmol) and powdered 4 Å molecular sieves. After stirring at room temperature for 4 h, sodium triacetoxyborohydride (171 mg, 0.80 mmol) was added and the resulting mixture stirred for a further 16 h. The reaction mixture was filtered through Celite®, loaded onto an Isolute® SCX-2 cartridge, the cartridge was washed with MeOH then the desired product eluted with 2 M NH3/MeOH in DCM. The resulting residue was purified by column chromatography (Si—PCC, 0-7% MeOH in DCM) to give the title compound as a pale yellow oil (44 mg, 28%). LCMS (Method H): RT=2.45 min, [M+H]+ 395.5

Workup

  1. stirringthe resulting mixture stirred for a further 16 h
  2. filtrationThe reaction mixture was filtered through Celite®
  3. washthe cartridge was washed with MeOH
  4. washthe desired product eluted with 2 M NH3/MeOH in DCM
  5. customThe resulting residue was purified by column chromatography (Si—PCC, 0-7% MeOH in DCM)

Sources & evidence

ORD record
ord-199c372b900049a5b025043682b5a25f
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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