Triethylamine → 3-(2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)-1-(tetrahydro-2H-pyran-4-yl)piperidin-3-ol

HRID 1946158Notes

Reaction equation

HRID 1946158 reaction equation
Cl.Cl.[CH2:3]([C:5]1[N:9]([C:10]2[N:18]=[C:17]3[C:13]([N:14]=[C:15]([C:20]4([OH:26])[CH2:25][CH2:24][CH2:23][NH:22][CH2:21]4)[N:16]3[CH3:19])=[C:12]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[N:11]=2)[C:8]2[CH:33]=[CH:34][CH:35]=[CH:36][C:7]=2[N:6]=1)[CH3:4].[O:37]1[CH2:42][CH2:41][CH2:40][CH2:39][C:38]1=O.CCN(CC)CC.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(Cl)Cl>[CH2:3]([C:5]1[N:9]([C:10]2[N:18]=[C:17]3[C:13]([N:14]=[C:15]([C:20]4([OH:26])[CH2:25][CH2:24][CH2:23][N:22]([CH:40]5[CH2:41][CH2:42][O:37][CH2:38][CH2:39]5)[CH2:21]4)[N:16]3[CH3:19])=[C:12]([N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[N:11]=2)[C:8]2[CH:33]=[CH:34][CH:35]=[CH:36][C:7]=2[N:6]=1)[CH3:4]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10953Delta-ValerolactoneHCID 5049666Sodium triacetoxyborohydrideHCID 674921803-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]piperidin-3-ol dihydrochloride

Product 1

HCID 596058873-(2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)-1-(tetrahydro-2H-pyran-4-yl)piperidin-3-olYield 81%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-[2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]piperidin-3-ol dihydrochloride from Example 746 (150 mg, 0.28 mmol), tetrahydropyran-2-one (39 μL, 0.42 mmol), NEt3 (78 μL, 0.56 mmol) and 4 Å powdered molecular sieves (300 mg) in DCE (3 mL) was stirred for 2 h before the addition of sodium triacetoxyborohydride (119 mg, 0.56 mmol). The resulting mixture was allowed to stir at r.t for 20 h then diluted with DCM and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%). The resulting residue was dissolved in DCM and treated with 4M HCl in dioxane. The resulting solid was triturated with Et2O and dried in vacuo affording 772 (124 mg, 72%). LCMS (method I): RT 2.52 min, [M+H]+ 547.2. 1H NMR (DMSO, 400 MHz): δ 9.36 (1 H, s), 8.18-8.14 (1 H, m), 7.80-7.79 (1 H, m), 7.50-7.48 (2 H, m), 4.28 (4 H, brd s), 4.10-3.90 (6 H, m), 3.78-3.77 (5 H, m), 3.43-3.39 (7 H, m), 3.25-3.10 (1 H, m), 2.30-1.65 (7 H, m), 1.44-1.38 (3 H, m)

Workup

  1. filtrationfiltered
  2. concentrationThe filtrate was concentrated in vacuo
  3. customthe residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%)
  4. dissolutionThe resulting residue was dissolved in DCM
  5. additiontreated with 4M HCl in dioxane
  6. customThe resulting solid was triturated with Et2O
  7. customdried in vacuo

Sources & evidence

ORD record
ord-2bd7f7f864d34d629ddd6e62a8e816b6
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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