Sodium triacetoxyborohydride → HCID 67492561, compound

HRID 1946104Notes

Reaction equation

HRID 1946104 reaction equation
[C@H:1]12[CH2:7][C@H:4]([NH:5][CH2:6]1)[CH2:3][N:2]2[CH2:8][C:9]1[N:10]([CH3:35])[C:11]2[C:16]([N:17]=1)=[C:15]([N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)[N:14]=[C:13]([N:24]1[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[N:26]=[C:25]1[CH2:33][CH3:34])[N:12]=2.[O:36]1[CH2:39][C:38](=O)[CH2:37]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH2:33]([C:25]1[N:24]([C:13]2[N:12]=[C:11]3[C:16]([N:17]=[C:9]([CH2:8][N:2]4[CH2:3][C@@H:4]5[CH2:7][C@H:1]4[CH2:6][N:5]5[CH:38]4[CH2:39][O:36][CH2:37]4)[N:10]3[CH3:35])=[C:15]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[N:14]=2)[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[N:26]=1)[CH3:34]

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 150242543-OxetanoneHCID 67492183HCID 67492183, compound

Product 1

HCID 67492561HCID 67492561, compoundYield 76.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of 8-[(1S,4S)-1-(2,5-diazabicyclo[2.2.1]hept-2-yl)methyl]-2-(2-ethyl-benzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine (250 mg, 0.53 mmol), oxetan-3-one (40 mg, 0.31 mmol) and molecular sieves (4 Å, powdered, 200 mg) in DCE (7 mL) was stirred at ambient temperature for 4 h. Sodium triacetoxyborohydride (148 mg, 0.70 mmol) was added and the mixture stirred for 16 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 90:0) to afford 598 as a white solid (125 mg, 45%). LCMS (method I): RT=2.39 min, M+H+=530. 1H NMR (CDCl3, 400 MHz) δ 8.02 (m, 1 H), 7.76 (m, 1 H), 7.26 (m, 2 H), 4.72-4.65 (m, 4 H), 4.34 (m, 4 H), 4.01-3.86 (m, 10 H), 3.35 (m, 4 H), 2.99 (m, 1 H), 2.82 (m, 1 H), 2.76 (m, 2 H), 1.79 (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 90:0)

Sources & evidence

ORD record
ord-fa3f7a459ddc4223b7236b2d95ab2112
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

Loading…