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 1923321Notes

Reaction equation

HRID 1923321 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-f880c78359dd43229f4ff28f0f8da006
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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