Sodium Carbonate → tert-butyl 1-(5-(5-(2,6-difluorophenyl)-1-tosyl-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate

HRID 1529335Notes

Reaction equation

HRID 1529335 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[N:14]=[C:13]2[C:15](I)=[CH:16][N:17]([S:18]([C:21]3[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=3)(=[O:20])=[O:19])[C:12]2=[CH:11][CH:10]=1.CC1(C)C(C)(C)OB([C:37]2[CH:38]=[C:39]([N:43]3[CH2:48][CH2:47][CH:46]([NH:49][C:50](=[O:56])[O:51][C:52]([CH3:55])([CH3:54])[CH3:53])[CH2:45][CH2:44]3)[CH:40]=[N:41][CH:42]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[N:14]=[C:13]2[C:15]([C:37]3[CH:38]=[C:39]([N:43]4[CH2:44][CH2:45][CH:46]([NH:49][C:50](=[O:56])[O:51][C:52]([CH3:54])([CH3:53])[CH3:55])[CH2:47][CH2:48]4)[CH:40]=[N:41][CH:42]=3)=[CH:16][N:17]([S:18]([C:21]3[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=3)(=[O:20])=[O:19])[C:12]2=[CH:11][CH:10]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 679596945-(2,6-difluorophenyl)-3-iodo-1-tosyl-1H-pyrrolo[3,2-b]pyridineHCID 67959870Tert-butyl 1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)piperidin-4-ylcarbamate

Product 1

HCID 67959812tert-butyl 1-(5-(5-(2,6-difluorophenyl)-1-tosyl-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-yl)piperidin-4-ylcarbamateYield 71.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 5-(2,6-difluorophenyl)-3-iodo-1-tosyl-1H-pyrrolo[3,2-b]pyridine (92 mg, 0.180 mmol), crude tert-butyl 1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)piperidin-4-ylcarbamate (127 mg, 0.316 mmol) and Pd(PPh3)4 (20.83 mg, 0.018 mmol, Strem) in toluene (1 mL) and Ethanol (1.000 mL) was treated with Na2CO3, 2.0 M (0.180 mL, 0.361 mmol). The reaction vessel was capped, degassed and backfilled with argon; and the reaction was heated to 100° C. After 20 h, the solution was cooled to 23° C., diluted with EtOAc (100 mL) and washed with brine (75 mL), dried over MgSO4, concentrated in vacuo and purified by silica gel chromatography (eluent: 30-90% EtOAc/hexane), affording tert-butyl 1-(5-(5-(2,6-difluorophenyl)-1-tosyl-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-yl)piperidin-4-ylcarbamate (85 mg, 71%). MS (ESI, pos. ion) m/z: 660.4 (M+1).

Workup

  1. customThe reaction vessel was capped
  2. customdegassed
  3. temperaturethe solution was cooled to 23° C.
  4. additiondiluted with EtOAc (100 mL)
  5. washwashed with brine (75 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. custompurified by silica gel chromatography (eluent: 30-90% EtOAc/hexane)

Sources & evidence

ORD record
ord-38735e874a2f4d5da7d68dd6b6061e08
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

Loading…