Sodium Carbonate → 2-Methyl-2-(4-((2-(2-methylbenzofuran-3-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)propanamide

HRID 1922903Notes

Reaction equation

HRID 1922903 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[C:5]2[S:10][C:9]([CH2:11][N:12]3[CH2:17][CH2:16][N:15]([C:18]([CH3:23])([CH3:22])[C:19]([NH2:21])=[O:20])[CH2:14][CH2:13]3)=[CH:8][C:6]=2[N:7]=1.CC1(C)C(C)(C)OB([C:38]2[C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=3[O:40][C:39]=2[CH3:47])O1.C(=O)([O-])[O-].[Na+].[Na+].C([O-])(=O)C.[K+]>C(#N)C.O.CCOC(C)=O>[CH3:22][C:18]([N:15]1[CH2:16][CH2:17][N:12]([CH2:11][C:9]2[S:10][C:5]3[C:4]([N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[N:3][C:2]([C:38]4[C:42]5[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=5[O:40][C:39]=4[CH3:47])=[N:7][C:6]=3[CH:8]=2)[CH2:13][CH2:14]1)([CH3:23])[C:19]([NH2:21])=[O:20]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 574940122-(4-((2-Chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-methylpropanamideHCID 673417654,4,5,5-Tetramethyl-2-(2-methylbenzofuran-3-yl)-1,3,2-dioxaborolane

Product 1

HCID 596058752-Methyl-2-(4-((2-(2-methylbenzofuran-3-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)propanamideYield 30.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

To a degassed suspension of 2-(4-((2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-methylpropanamide (90.0 mg 0.205 mmol), 4,4,5,5-tetramethyl-2-(2-methylbenzofuran-3-yl)-1,3,2-dioxaborolane (120 mg, 0.46 mmol) in acetonitrile (2 mL) was added 2 M aqueous solution of sodium carbonate (0.20 mL) and 1M aqueous solution of potassium acetate (0.2 mL). The mixture was then heated in a microwave at 140° C. for 30 minutes. The reaction mixture was diluted with water and EtOAc. The aqueous layer was extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by RP-HPLC to give 140 (33.6 mg, 30.6%). LCMS: M+H+=535.2. 1H-NMR (400 MHz, DMSO-d6): δ 8.45 (m, 1H), 7.55 (m, 1H), 7.42 (s, 1H), 7.31 (m, 2H), 7.05 (s, 1H), 6.93 (s, 1H), 3.95 (m, 4H), 3.86 (s, 2H), 3.83 (m, 4H), 2.84 (s, 3H), 2.42-2.63 (m, 8H), 1.08 (s, 6H)

Workup

  1. extractionThe aqueous layer was extracted with EtOAc
  2. washThe combined extracts were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by RP-HPLC

Sources & evidence

ORD record
ord-55b2b52a1e8644258d913127c39c767c
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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