Tetrahydro-4H-pyran-4-one → HCID 59606081, compound

HRID 1923340Notes

Reaction equation

HRID 1923340 reaction equation
[NH:1]1[CH2:4][CH:3]([C:5]2[N:6]([CH3:31])[C:7]3[C:12]([N:13]=2)=[C:11]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[N:10]=[C:9]([N:20]2[C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=4[N:22]=[C:21]2[CH2:29][CH3:30])[N:8]=3)[CH2:2]1.[O:32]1[CH2:37][CH2:36][C:35](=O)[CH2:34][CH2:33]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH2:29]([C:21]1[N:20]([C:9]2[N:8]=[C:7]3[C:12]([N:13]=[C:5]([CH:3]4[CH2:2][N:1]([CH:35]5[CH2:36][CH2:37][O:32][CH2:33][CH2:34]5)[CH2:4]4)[N:6]3[CH3:31])=[C:11]([N:14]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[N:10]=2)[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[N:22]=1)[CH3:30]

Participants

5

Reactant 3

HCID 121599Tetrahydro-4H-pyran-4-oneHCID 5049666Sodium triacetoxyborohydrideHCID 59605649HCID 59605649, compound

Product 1

HCID 59606081HCID 59606081, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 4-(8-(azetidin-3-yl)-2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-9H-purin-6-yl)morpholine 680 (100 mg, 0.24 mmol), tetrahydropyran-4-one (34 mg, 0.33 mmol) and 4 Å powdered molecular sieves (130 mg) in DCE (3 mL) was stirred for 5.5 h before the addition of sodium triacetoxyborohydride (101 mg, 0.48 mmol). The resulting mixture was allowed to stir for 16 h at r.t, then filtered through Celite®, washing with DCM. The filtrate was washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, MeOH:EtOAc, 0-30%) followed by Isolute® SCX-2 cartridge which was washed with MeOH/DCM and the product eluted with 2M NH3/MeOH. The resulting solid was triturated with EtOAc affording 747 as a white powder (37 mg, 31%). LCMS (method I): RT 2.46 min, [M+H]+ 503.1. 1H NMR (CDCl3, 400 MHz): δ 8.01-7.97 (1 H, m), 7.75-7.74 (1 H, m), 7.26 (2 H, s), 4.37 (4 H, s), 4.02-3.80 (9 H, m), 3.70 (3 H, s), 3.51-3.37 (4 H, m), 3.34 (2 H, q, J=7.48 Hz), 2.41-2.33 (1 H, m), 1.77-1.66 (3 H, m), 1.43 (4 H, t, J=7.47 Hz)

Workup

  1. filtrationfiltered through Celite®
  2. washwashing with DCM
  3. washThe filtrate was washed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by column chromatography (Si-PCC, MeOH:EtOAc, 0-30%)
  7. washwas washed with MeOH/DCM
  8. washthe product eluted with 2M NH3/MeOH
  9. customThe resulting solid was triturated with EtOAc affording 747 as a white powder (37 mg, 31%)
  10. customRT 2.46 min, [M+H]+ 503.1

Sources & evidence

ORD record
ord-378cb983010544acb35a42a2d26e067e
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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