Sodium Carbonate → 1-((2-(1H-indol-3-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-N,N-dimethylpiperidin-4-amine

HRID 1692866Notes

Reaction equation

HRID 1692866 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.C([N:34]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:36](B(O)O)=[CH:35]1)(OC(C)(C)C)=O.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>[NH:34]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:36]([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)=[CH:35]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 52330101-(tert-Butoxycarbonyl)indole-3-boronic acidHCID 575067401-((2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-N,N-dimethylpiperidin-4-amine

Product 1

HCID 498208261-((2-(1H-indol-3-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-N,N-dimethylpiperidin-4-amineYield 27%

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 (0.500 g, 1.26 mmol), 1-BOC-indole-3-yl-boronic acid (363 mg, 1.39 mmol), 1 N sodium carbonate solution (3 mL), acetonitrile (9 mL) and Pd(dppf)Cl2 (103 mg. 0.126 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) followed by trituration with hot ethanol afforded 101 (161 mg, 27%) as a cream powder. MS m/e 477 [M+H]+. 1H NMR (400 MHz, CHCl3-d) δ ppm 1.53-1.68 (m, 2H) 1.75 (br. s., 1H) 1.83 (d, J=11.6 Hz, 2H) 2.05-2.22 (m, 3H) 2.30 (s, 6H) 3.04 (d, J=12.1 Hz, 2H) 3.81 (s, 2H) 3.88-3.99 (m, 4H) 4.01-4.13 (m, 4H) 7.21-7.32 (m, 2H) 7.37-7.45 (m, 1H) 8.14 (d, J=2.5 Hz, 1H) 8.64-8.70 (m, 1H) 8.76 (br. s., 1H)

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-07cb3890d57e49ce8cb5ebbf21d766a5
Source dataset
uspto-grants-2012_04
Patent number
US08158625B2

Reaction notes

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