Dichloromethane → HCID 58709962, compound

HRID 2375883Notes

Reaction equation

HRID 2375883 reaction equation
I[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[C:12]3[CH:19]=[C:18]([C:20]4[CH2:21][CH2:22][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:24][CH:25]=4)[NH:17][C:13]=3[N:14]=[CH:15][N:16]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[S:33]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34]1.C(=O)([O-])[O-].[K+].[K+].ClCCl>O1CCOCC1.O.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]>[CH3:9][O:8][C:7]1[CH:6]=[CH:5][C:4]([NH:10][C:11]2[C:12]3[CH:19]=[C:18]([C:20]4[CH2:21][CH2:22][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:24][CH:25]=4)[NH:17][C:13]=3[N:14]=[CH:15][N:16]=2)=[CH:3][C:2]=1[C:35]1[CH:36]=[CH:37][S:33][CH:34]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 581760Thiophene-3-boronic acidHCID 58710073HCID 58710073, compound

Product 1

HCID 58709962HCID 58709962, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

To a stirred solution of tert-butyl 4-[4-(3-iodo-4-methoxyphenylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridine-1-carboxylate (82.1 mg, 0.15 mmol), 3-thienylboronic acid (28.8 mg, 0.225 mmol) and potassium carbonate (41.5 mg, 0.3 mmol) in dioxane/water (4:1) (1.0 mL) was added [1,1′-bis(diphenylphosphino)ferrocene]dichloro-palladium(II), complex with dichloromethane (1:1) (12 mg, 0.015 mmol). The resulting mixture was bubbled N2 for 5 min and then heated at reflux for 16 h. After cooled to rt, the solvents were removed under reduced pressure. The residue was dissolved in DMF (2 mL). The DMF solution was filtered and purified by HPLC to give the title compound. 1H-NMR (DMSO-d6, 400 MHz): δ=1.43 (s, 9H), 3.56 (m, 2H), 3.82 (s, 3H), 4.03 (m, 2H), 6.38 (s, br, 1H), 6.73 (s, 1H), 7.09 (d, J=9.2 Hz, 1H), 7.45 (dd, J=0.8, 5.2 Hz, 1H), 7.60 (dd, J=2.8, 4.8 Hz, 1H), 7.76 (m, 1H), 7.80 (dd, J=2.8, 8.8 Hz, 1H), 7.94 (d, J=2.8 Hz, 1H), 8.22 (s, 1H), 9.26 (s, 1H), 11.90 (s, 1H). MS (ES+): m/z 504.05 [MH+]. HPLC: tR=3.22 min (ZQ2000, polar—5 min).

Workup

  1. customThe resulting mixture was bubbled N2 for 5 min
  2. temperatureheated
  3. temperatureat reflux for 16 h
  4. customthe solvents were removed under reduced pressure
  5. dissolutionThe residue was dissolved in DMF (2 mL)
  6. filtrationThe DMF solution was filtered
  7. custompurified by HPLC

Sources & evidence

ORD record
ord-28125e73ce264ba18bcfab8ff4a0caa8
Source dataset
uspto-grants-2008_12
Patent number
US07465726B2

Reaction notes

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