Sodium Carbonate → HCID 59605657, compound

HRID 1922907Notes

Reaction equation

HRID 1922907 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[C:5]2[S:10][C:9]([CH2:11][N:12]3[CH2:17][CH2:16][CH:15]([N:18]([CH3:20])[CH3:19])[CH2:14][CH2:13]3)=[CH:8][C:6]=2[N:7]=1.[S:27]1[CH:31]=[C:30](B(O)O)[C:29]2[CH:35]=[CH:36][CH:37]=[CH:38][C:28]1=2.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(#N)C>[S:27]1[CH:31]=[C:30]([C:2]2[N:3]=[C:4]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[C:5]3[S:10][C:9]([CH2:11][N:12]4[CH2:17][CH2:16][CH:15]([N:18]([CH3:20])[CH3:19])[CH2:14][CH2:13]4)=[CH:8][C:6]=3[N:7]=2)[C:29]2[CH:35]=[CH:36][CH:37]=[CH:38][C:28]1=2

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2776344(1-Benzothiophen-3-yl)boronic acidHCID 575067401-((2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-N,N-dimethylpiperidin-4-amine

Product 1

HCID 59605657HCID 59605657, compoundYield 48.2%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
140 °C

Procedure

A microwave vessel was charged with [1-(2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-piperidin-4-yl]-dimethyl-amine (0.400 g, 1.01 mmol), benzo[b]thien-3-ylboronic acid (197 mg, 1.11 mmol), 1 N sodium carbonate solution (2.5 mL), acetonitrile (7.5 mL) and Pd(dppf)Cl2 (82.4 mg. 0.100 mmol), then the mixture was degassed, sealed, and heated at 140° C. under microwave irradiation for 20 min. The reaction mixture was diluted with dichloromethane (100 mL) and 1 N sodium carbonate solution (10 mL) then the phases were separated. The organic phase was washed with saturated aqueous sodium bicarbonate solution (15 mL) then dried (MgSO4) and concentrated in vacuo. Purification by chromatography (silica, 0 to 15% of a 9.5:0.5 MeOH:NH4OH solution in dichloromethane) to afford 146 (240 mg, 48.2%) as a light brown solid. MS m/e 494 [M+H]+ 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.47-1.68 (m, 2 H) 1.81 (d, J=12.43 Hz, 2 H) 2.03-2.20 (m, 3 H) 2.28 (s, 6 H) 3.02 (d, J=12.06 Hz, 2 H) 3.80 (s, 2 H) 3.85-3.95 (m, 4 H) 3.99-4.10 (m, 4 H) 7.32 (s, 1 H) 7.34-7.42 (m, 1 H) 7.43-7.53 (m, 1H) 7.89 (d, J=7.91 Hz, 1 H) 8.44 (s, 1 H) 9.00-9.15 (m, 1 H).

Workup

  1. customthe mixture was degassed
  2. customsealed
  3. additionThe reaction mixture was diluted with dichloromethane (100 mL) and 1 N sodium carbonate solution (10 mL)
  4. customthe phases were separated
  5. washThe organic phase was washed with saturated aqueous sodium bicarbonate solution (15 mL)
  6. dry with materialthen dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customPurification by chromatography (silica, 0 to 15% of a 9.5:0.5 MeOH:NH4OH solution in dichloromethane)

Sources & evidence

ORD record
ord-d0ac4c6d940e4bbeb3cdcc9bf3d485a9
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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