Sodium triacetoxyborohydride → HCID 59605800, compound

HRID 1923095Notes

Reaction equation

HRID 1923095 reaction equation
[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([CH:18]=O)[N:14]3[CH3:17])=[C:10]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[N:9]=2)[C:6]2[CH:26]=[CH:27][CH:28]=[CH:29][C:5]=2[N:4]=1)[CH3:2].[NH:30]1[CH2:33][CH:32]([C:34]([N:36]2[CH2:40][CH2:39][CH2:38][CH2:37]2)=[O:35])[CH2:31]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([CH2:18][N:30]4[CH2:31][CH:32]([C:34]([N:36]5[CH2:37][CH2:38][CH2:39][CH2:40]5)=[O:35])[CH2:33]4)[N:14]3[CH3:17])=[C:10]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[N:9]=2)[C:6]2[CH:26]=[CH:27][CH:28]=[CH:29][C:5]=2[N:4]=1)[CH3:2]

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 59605320(Azetidin-3-yl)(pyrrolidin-1-yl)methanoneHCID 596059872-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde

Product 1

HCID 59605800HCID 59605800, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (100 mg, 0.27 mmol) and azetidin-3-ylpyrrolidin-1-ylmethanone (50 mg, 0.32 mmol) in DCE (3 mL) was stirred at ambient temperature for 90 min. Sodium triacetoxyborohydride (86 mg, 0.41 mmol) was added and the mixture stirred for 18 h, then loaded onto an Isolute® SCX-2 cartridge (10 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, EtOAc:MeOH; gradient from 100:0 to 70:30) followed by reverse phase HPLC (Phenomenex Gemini 5u C18, 20 mM triethylamine in water on a gradient of acetonitrile 80:20 to 2:98) to afford 365 as a white solid (65 mg, 48%). LCMS (Method G): RT=6.26 min, M+H+=530. 1H NMR (CDCl3, 400 MHz) δ 8.01 (m, 1 H); 7.73 (m, 1 H); 7.27 (m, 2 H); 4.35 (m, 4 H); 3.86 (m, 6 H); 3.83 (s, 3 H); 3.69-3.63 (m, 2 H); 3.55-3.42 (m, 5 H); 3.39-3.27 (m, 4 H); 1.98-1.82 (m, 4 H) and 1.44 (t, J=7.5 Hz, 3 H)

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, EtOAc:MeOH; gradient from 100:0 to 70:30)

Sources & evidence

ORD record
ord-1b3640e1c8124f0a95f45ee4cf57f949
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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