Potassium Carbonate → Benzothiazol-6-yl-[6-(1,2,3,6-tetrahydropyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine trihydrochloride

HRID 2375826Notes

Reaction equation

HRID 2375826 reaction equation
[S:1]1[C:5]2[CH:6]=[C:7]([NH:10][C:11]3[C:12]4[CH:19]=[C:18](I)[NH:17][C:13]=4[N:14]=[CH:15][N:16]=3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.C(OC([N:28]1[CH2:33][CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH2:30][CH2:29]1)=O)(C)(C)C.C(=O)([O-])[O-].[K+].[K+].[ClH:49].O1CCOCC1>COCCOC.O.C(Cl)Cl.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]>[ClH:49].[ClH:49].[ClH:49].[S:1]1[C:5]2[CH:6]=[C:7]([NH:10][C:11]3[C:12]4[CH:19]=[C:18]([C:31]5[CH2:32][CH2:33][NH:28][CH2:29][CH:30]=5)[NH:17][C:13]=4[N:14]=[CH:15][N:16]=3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 204431481,4-Dioxane hydrochlorideHCID 58710006Benzothiazol-6-yl-(6-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine

Product 1

HCID 69274170Benzothiazol-6-yl-[6-(1,2,3,6-tetrahydropyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine trihydrochloride

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent3×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of benzothiazol-6-yl-(6-iodo-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (4.05 g, 10.3 mmol) in 1,2-dimethoxyethane (125 mL) and water (25 mL) were added 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (3.50 g, 11.3 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloro palladium(II), complex with dichloromethane (1:1) (420 mg, 0.51 mmol) and potassium carbonate (2.85 g, 20.6 mmol). The flask was evacuated and refilled with N2 (3×). The mixture was heated at 80° C. overnight. The reaction mixture was diluted with EtOAc (200 mL) and water (50 mL) and filtered through a pad of celite. The organic phase was separated, and the aqueous phase was extracted with EtOAc (2×50 mL). The combined organic phases were washed with brine (100 mL), and dried over anhydrous sodium sulfate. Evaporation under reduced pressure afforded a brown solid. To a suspension of this crude material in methylene chloride (30 mL) was added 4M HCl/1,4-dioxane (30 mL), and the resulting mixture was stirred at rt overnight. The mixture was diluted with CH2Cl2 (30 mL), and the light-yellow solid was collected by filtration and dried in vacuo to give the title compound. LC-MS (ES, Pos.): 349 [MH+]. 1H NMR (DMSO-d6, 400 MHz): δ=2.51 (m, 2H), 3.34 (m, 2H), 3.81 (m, 2H), 6.52 (s, 1H), 7.09 (s, 1H), 7.73 (dd, J=8.7 Hz, 2.0 Hz, 1H), 8.22 (d, J=8.7 Hz, 1H), 8.36 (d, J=2.0 Hz, 1H), 8.51 (s, 1H), 9.46 (s, 1H).

Workup

  1. customThe flask was evacuated
  2. additionrefilled with N2 (3×)
  3. additionThe reaction mixture was diluted with EtOAc (200 mL) and water (50 mL)
  4. filtrationfiltered through a pad of celite
  5. customThe organic phase was separated
  6. extractionthe aqueous phase was extracted with EtOAc (2×50 mL)
  7. washThe combined organic phases were washed with brine (100 mL)
  8. dry with materialdried over anhydrous sodium sulfate
  9. customEvaporation under reduced pressure
  10. customafforded a brown solid
  11. filtrationthe light-yellow solid was collected by filtration
  12. customdried in vacuo

Sources & evidence

ORD record
ord-becea08d7e7648e0aa3791e3c89659f4
Source dataset
uspto-grants-2008_12
Patent number
US07465726B2

Reaction notes

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