Dichloromethane → HCID 58710067, compound

HRID 2375882Notes

Reaction equation

HRID 2375882 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].C([N:40]1[CH:44]=[CH:43][CH:42]=[C:41]1B(O)O)(OC(C)(C)C)=O.C(=O)([O-])[O-].[K+].[K+].C(Cl)Cl.[OH-].[Na+]>O1CCOCC1.O.CO.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:41]1[NH:40][CH:44]=[CH:43][CH:42]=1

Participants

9

Reactant 5

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 27343211-(tert-Butoxycarbonyl)-2-pyrroleboronic AcidHCID 58710073HCID 58710073, compound

Product 1

HCID 58710067HCID 58710067, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 887MethanolSolventHCID 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), N-Boc-2-pyrrolylboronic acid (47.5 mg, 0.225 mmol) and potassium carbonate (41.5 mg, 0.3 mmol) in dioxane/water (4:1) (11.0 mL) was added PdCl2(dppf).CH2Cl2 (12.2 mg, 0.015 mmol). The mixture was heated at reflux for 18 h. Solvents were removed and the residue was dissolved in DMF (≈2 mL). The DMF solution was filtered and sent to mass-directed HPLC purification. The pyrrole-Boc-protected product obtained was stirred with NaOH (s, 369 mg) in 9 mL of methanol at rt for 17 h. The solvent was removed and the residue was dissolved in DMF (1.5 mL) and purified by HPLC purification to give the title compound. 1H-NMR (DMSO-d6, 400 MHz): δ=1.43 (s, 9H), 2.46 (m, 2H), 3.56 (m, 2H), 3.87 (s, 3H), 4.03 (m, 2H), 6.11 (q, J=2.4 Hz, 1H), 6.37 (s, br, 1H), 6.49 (s, 1H), 6.71 (s, 1H), 6.81 (q, J=2.4 Hz, 1H), 7.04 (d, J=9.2 Hz, 1H), 7.63 (d, J=6.0 Hz, 1H), 7.92 (d, J=2.4 Hz, 1H), 8.20 (d, J=4.4 Hz, 1H), 9.22 (s, 1H), 10.91 (s, 1H), 11.89 (s, 1H). MS (ES+): m/z 487.04 [MH+]. HPLC: tR=2.96 min (ZQ2000, polar—5 min).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 18 h
  3. customSolvents were removed
  4. dissolutionthe residue was dissolved in DMF (≈2 mL)
  5. filtrationThe DMF solution was filtered
  6. customsent to mass-directed HPLC purification
  7. customobtained
  8. customThe solvent was removed
  9. dissolutionthe residue was dissolved in DMF (1.5 mL)
  10. custompurified by HPLC purification

Sources & evidence

ORD record
ord-7a03a3ba3ee742d6b41f6b8fad74c55c
Source dataset
uspto-grants-2008_12
Patent number
US07465726B2

Reaction notes

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