Sodium triacetoxyborohydride → HCID 59605860, compound

HRID 1923112Notes

Reaction equation

HRID 1923112 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].[N:30]1([C:34]([C@H:36]2[CH2:40][CH2:39][NH:38][CH2:37]2)=[O:35])[CH2:33][CH2:32][CH2:31]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[N:30]1([C:34]([C@H:36]2[CH2:40][CH2:39][N:38]([CH2:18][C:13]3[N:14]([CH3:17])[C:15]4[C:11]([N:12]=3)=[C:10]([N:20]3[CH2:21][CH2:22][O:23][CH2:24][CH2:25]3)[N:9]=[C:8]([N:7]3[C:6]5[CH:26]=[CH:27][CH:28]=[CH:29][C:5]=5[N:4]=[C:3]3[CH2:1][CH3:2])[N:16]=4)[CH2:37]2)=[O:35])[CH2:31][CH2:32][CH2:33]1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 59605586HCID 59605586, compoundHCID 596059872-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde

Product 1

HCID 59605860HCID 59605860, compoundYield 46%

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, 0.26 mmol) and azetidin-1-yl-(S)-pyrrolidin-3-ylmethanone (47 mg, 0.31 mmol) in DCE (5 mL) was stirred at ambient temperature for 4 h. Sodium triacetoxyborohydride (81 mg, 0.38 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, DCM: 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 393 as a white solid (62 mg, 46%). LCMS (Method G): RT=5.93 min, M+H+=530. 1H NMR (CDCl3, 400 MHz) δ 8.02 (m, 1 H); 7.75 (m, 1 H); 7.29-7.22 (m, 2 H); 4.35 (m, 4 H); 4.22-4.08 (m, 2 H); 4.02 (t, J=7.9 Hz, 2H); 3.94 (s, 2H); 3.90-3.83 (m, 7 H); 3.35 (q, J=7.5 Hz, 2 H); 3.09-2.57 (m, 5 H); 2.33-2.23 (m, 2 H); 2.09 (m, 2 H) and 1.45 (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, DCM: MeOH; gradient from 100:0 to 70:30)

Sources & evidence

ORD record
ord-5c809eda94ed4df7a44d8c66d1241102
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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