Sodium triacetoxyborohydride → 2-Chloro-9-methyl-6-morpholin-4-yl-8-(4-oxetan-3-ylpiperidin-1-ylmethyl)-9H-purine

HRID 1922821Notes

Reaction equation

HRID 1922821 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][CH2:15]2)[N:3]=1.[O:20]1[CH2:23][CH:22]([CH:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)[CH2:21]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][N:27]3[CH2:28][CH2:29][CH:24]([CH:22]4[CH2:23][O:20][CH2:21]4)[CH2:25][CH2:26]3)[N:8]2[CH3:11])=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[N:3]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 552642454-(Oxetan-3-yl)piperidineHCID 596034722-Chloro-9-methyl-6-morpholino-9H-purine-8-carbaldehyde

Product 1

HCID 596054062-Chloro-9-methyl-6-morpholin-4-yl-8-(4-oxetan-3-ylpiperidin-1-ylmethyl)-9H-purineYield 57%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-chloro-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (1.0 g, 3.55 mmol), 4-oxetan-3-ylpiperidine (600 mg, 4.25 mmol) and molecular sieves (4 Å, powdered, 5 g) in anhydrous THF (25 mL) was stirred at ambient temperature for 5 h. Sodium triacetoxyborohydride (1.5 g, 7.08 mmol) was added and the mixture stirred for 18 h, then loaded onto an Isolute® SCX-2 cartridge (25 g). The cartridge was then washed with methanol and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH; 100:0 to 99:1 to 98:2 to 95:5 to 90:10) to afford the title compound as a white foam (0.82 g, 57%). LCMS (Method H): RT=2.38 min, M+H+=408.

Workup

  1. washThe cartridge was then washed with methanol
  2. washthe desired product was subsequently eluted
  3. customThe product was collected
  4. concentrationconcentrated in vacuo
  5. customThe resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH; 100:0 to 99:1 to 98:2 to 95:5 to 90:10)

Sources & evidence

ORD record
ord-4a996e2692994ffbba4e3d1ca3106302
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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