Sodium triacetoxyborohydride → 2-(1-(9-methyl-6-morpholino-8-((4-(oxetan-3-yl)piperidin-1-yl)methyl)-9H-purin-2-yl)-1H-benzo[d]imidazol-2-yl)ethanol

HRID 1923199Notes

Reaction equation

HRID 1923199 reaction equation
[OH:1][CH2:2][CH2:3][C:4]1[N:8]([C:9]2[N:17]=[C:16]3[C:12]([N:13]=[C:14]([CH:19]=O)[N:15]3[CH3:18])=[C:11]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[N:10]=2)[C:7]2[CH:27]=[CH:28][CH:29]=[CH:30][C:6]=2[N:5]=1.[O:31]1[CH2:34][CH:33]([CH:35]2[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)[CH2:32]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:18][N:15]1[C:14]([CH2:19][N:38]2[CH2:39][CH2:40][CH:35]([CH:33]3[CH2:34][O:31][CH2:32]3)[CH2:36][CH2:37]2)=[N:13][C:12]2[C:16]1=[N:17][C:9]([N:8]1[C:7]3[CH:27]=[CH:28][CH:29]=[CH:30][C:6]=3[N:5]=[C:4]1[CH2:3][CH2:2][OH:1])=[N:10][C:11]=2[N:21]1[CH2:22][CH2:23][O:24][CH2:25][CH2:26]1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 552642454-(Oxetan-3-yl)piperidineHCID 596052312-[2-(2-Hydroxyethyl)benzoimidazol-1-yl]-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde

Product 1

HCID 596053362-(1-(9-methyl-6-morpholino-8-((4-(oxetan-3-yl)piperidin-1-yl)methyl)-9H-purin-2-yl)-1H-benzo[d]imidazol-2-yl)ethanolYield 20%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of 2-[2-(2-hydroxyethyl)benzoimidazol-1-yl]-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (200 mg, 0.49 mmol), 4-oxetan-3-ylpiperidine (83 mg, 0.59 mmol) and molecular sieves (4 Å, powdered, 1 g) in DCE (5 mL) was stirred at ambient temperature for 5 h. Sodium triacetoxyborohydride (156 mg, 0.74 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; 100:0 to 99:1 to 98:2 to 97:3 to 95:5) to afford 512 as a white solid (51 mg, 20%). LCMS (Method I): RT=2.39 min, M+H+=533. 1H NMR (CDCl3, 400 MHz) δ 8.04 (m, 1 H); 7.75 (m, 1 H); 7.33 (m, 2 H); 4.76 (dd, J=7.8, 6.0 Hz, 2 H); 4.45 (t, J=6.0 Hz, 2 H); 4.35 (m, 4 H); 4.19 (t, J=5.5 Hz, 2 H); 3.94-3.80 (m, 9 H); 3.54 (t, J=5.5 Hz, 2 H); 3.02 (m, 2 H); 2.81-2.72 (m, 1 H); 2.29 (m, 2 H); 1.71 (m, 5 H) and 1.28 (m, 1 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; 100:0 to 99:1 to 98:2 to 97:3 to 95:5)

Sources & evidence

ORD record
ord-f9d6ef420bc445b886cdc942d2555e5d
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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