Sodium Iodide → 2-(3-(2-(2-isopropyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)-3-methoxypiperidin-1-yl)acetamide

HRID 1946132Notes

Reaction equation

HRID 1946132 reaction equation
[CH:1]([C:4]1[N:8]([C:9]2[N:17]=[C:16]3[C:12]([N:13]=[C:14]([C:19]4([O:25][CH3:26])[CH2:24][CH2:23][CH2:22][NH:21][CH2:20]4)[N:15]3[CH3:18])=[C:11]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[N:10]=2)[C:7]2[CH:33]=[CH:34][CH:35]=[CH:36][C:6]=2[N:5]=1)([CH3:3])[CH3:2].Br[CH2:38][C:39]([NH2:41])=[O:40].[I-].[Na+].C([O-])([O-])=O.[K+].[K+]>CC#N.CCOC(C)=O>[CH:1]([C:4]1[N:8]([C:9]2[N:17]=[C:16]3[C:12]([N:13]=[C:14]([C:19]4([O:25][CH3:26])[CH2:24][CH2:23][CH2:22][N:21]([CH2:38][C:39]([NH2:41])=[O:40])[CH2:20]4)[N:15]3[CH3:18])=[C:11]([N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[N:10]=2)[C:7]2[CH:33]=[CH:34][CH:35]=[CH:36][C:6]=2[N:5]=1)([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 696322-BromoacetamideHCID 596052822-(2-Isopropylbenzoimidazol-1-yl)-8-(3-methoxypiperidin-3-yl)-9-methyl-6-morpholin-4-yl-9H-purine

Product 1

HCID 596057072-(3-(2-(2-isopropyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)-3-methoxypiperidin-1-yl)acetamide

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-(2-isopropylbenzoimidazol-1-yl)-8-(3-methoxypiperidin-3-yl)-9-methyl-6-morpholin-4-yl-9H-purine from Example 713 (1.0 g, 2.10 mmol), 2-bromoacetamide (290 mg, 2.10 mmol), sodium iodide (32 mg, 0.21 mmol) and K2CO3 (610 mg, 4.41 mmol) in MeCN (20 mL) was stirred at r.t. for 66 h. The reaction mixture was diluted with EtOAc, filtered and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%) then triturated with Et2O affording 716 (675 mg, 59%). LCMS (method I): RT 2.66 min, [M+H]+ 548.2. 1H NMR (DMSO, 400 MHz): δ 7.93-7.92 (1 H, m), 7.66-7.62 (1 H, m), 7.26-7.22 (2 H, m), 7.14 (1 H, s), 7.07 (1 H, s), 4.26 (4 H, brd s), 3.98-3.88 (4 H, m), 3.80-3.75 (4 H, m), 3.10-3.00 (4 H, m), 3.00-2.90 (3 H, m), 2.70-2.60 (1 H, m), 2.45-2.35 (1 H, m), 2.15-1.95 (2 H, m), 1.95-1.77 (1 H, m), 1.78-1.68 (1 H, m), 1.37-1.37 (6 H, m)

Workup

  1. filtrationfiltered
  2. concentrationconcentrated in vacuo
  3. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%)
  4. customthen triturated with Et2O affording 716 (675 mg, 59%)
  5. customRT 2.66 min, [M+H]+ 548.2

Sources & evidence

ORD record
ord-2794eb0b290c488ca2cd5aeaf494a1c6
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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