Sodium triacetoxyborohydride → HCID 59605559, compound

HRID 1945905Notes

Reaction equation

HRID 1945905 reaction equation
[CH3:1][N:2]1[C:10]([CH:11]=O)=[N:9][C:8]2[C:3]1=[N:4][C:5]([N:19]1[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[N:21]=[C:20]1[CH3:28])=[N:6][C:7]=2[N:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.[CH3:29][CH:30]([CH3:39])[CH:31]([CH:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1)[OH:32].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:29][CH:30]([CH3:39])[CH:31]([CH:33]1[CH2:38][CH2:37][N:36]([CH2:11][C:10]2[N:2]([CH3:1])[C:3]3[C:8]([N:9]=2)=[C:7]([N:13]2[CH2:14][CH2:15][O:16][CH2:17][CH2:18]2)[N:6]=[C:5]([N:19]2[C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=4[N:21]=[C:20]2[CH3:28])[N:4]=3)[CH2:35][CH2:34]1)[OH:32]

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 232831512-Methyl-1-(piperidin-4-yl)propan-1-olHCID 596054202-(2-methylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde

Product 1

HCID 59605559HCID 59605559, compoundYield 41.5%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 9-methyl-2-(2-methylbenzoimidazol-1-yl)-6-morpholin-4-yl-9H-purine-8-carbaldehyde (200 mg, 0.53 mmol), 2-methyl-1-piperidin-4-yl-propan-1-ol (125 mg, 0.79 mmol) and 4 Å molecular sieves (1.0 g) in 1,2-dichloroethane (10 mL) was stirred at RT under nitrogen atmosphere for 1.5 h. Sodium triacetoxyborohydride (167 mg, 0.79 mmol) was added and the resulting reaction mixture was stirred at RT for 16 h. The solvent was reduced in vacuo and the residue was loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was washed with DCM/MeOH, the desired product was subsequently eluted using a mixture of 2M NH3 in MeOH and DCM. The residue was purified by column chromatography (Si—PCC, MeOH:DCM: gradient 0:100 to 5:95) followed by a further purification (Si—PCC, acetone:cyclohexane: gradient 10:90 to 40:60). The solvents were reduced in vacuo to afford 346 as a white solid (114 mg, 41%). LCMS (Method G): RT 6.81 min, [M+H]+ 519. 1H NMR (400 MHz, CH3OH-d4): δ 8.06-8.05 (1 H, m), 7.56-7.55 (1 H, m), 7.25-7.24 (2 H, m), 4.29 (4 H, br s), 3.84 (3 H, s), 3.81 (4 H, t, J=4.74 Hz), 3.74 (2 H, s), 2.98-2.95 (3 H, m), 2.86 (3 H, s), 2.11 (2 H, m), 1.84 (1 H, m), 1.72-1.71 (1 H, m), 1.57-1.20 (4 H, m), 0.87 (6 H, dd, J=15.35, 6.73 Hz)

Workup

  1. customthe resulting reaction mixture
  2. stirringwas stirred at RT for 16 h
  3. washThe cartridge was washed with DCM/MeOH
  4. washthe desired product was subsequently eluted
  5. additiona mixture of 2M NH3 in MeOH and DCM
  6. customThe residue was purified by column chromatography (Si—PCC, MeOH:DCM: gradient 0:100 to 5:95)
  7. customfollowed by a further purification (Si—PCC, acetone:cyclohexane: gradient 10:90 to 40:60)

Sources & evidence

ORD record
ord-138b6cc8ebad4d8c942d1162afc6e2d1
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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