Sodium Carbonate → tert-butyl 3-(5-(5-(2,6-difluorophenyl)-1-tosyl-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-ylamino)piperidine-1-carboxylate

HRID 1529339Notes

Reaction equation

HRID 1529339 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]([NH:43][CH:44]3[CH2:49][CH2:48][CH2:47][N:46]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:45]3)[CH:40]=[N:41][CH:42]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCO.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]([NH:43][CH:44]4[CH2:49][CH2:48][CH2:47][N:46]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:45]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 67959896Tert-butyl 3-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-ylamino)piperidine-1-carboxylate

Product 1

HCID 67959766tert-butyl 3-(5-(5-(2,6-difluorophenyl)-1-tosyl-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-ylamino)piperidine-1-carboxylateYield 35%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 5-(2,6-difluorophenyl)-3-iodo-1-tosyl-1H-pyrrolo[3,2-b]pyridine (73 mg, 0.143 mmol) and crude tert-butyl 3-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-ylamino)piperidine-1-carboxylate (113 mg, 0.279 mmol) in toluene (1.000 mL) and EtOH (1 mL) was treated with Na2CO3, 2.0 M (0.143 mL, 0.286 mmol) and Pd(PPh3)4 (16.53 mg, 0.014 mmol, Strem). The reaction mixture was degassed, backfilled with argon and heated to 100° C. under N2. After 15 h, the reaction was cooled to 23° C., filtered through celite, and purified by silica gel chromatography (eluent: 0.5-10% MeOH/DCM), affording tert-butyl 3-(5-(5-(2,6-difluorophenyl)-1-tosyl-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-ylamino)piperidine-1-carboxylate (Rf=0.5 in 10% MeOH/DCM, desired product) (33 mg, 35%); along with a byproduct, tert-butyl 3-(5-(5-(2,6-difluorophenyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)pyridin-3-ylamino)piperidine-1-carboxylate (Rf=0.2 in 10% MeOH/DCM, de-tosylated product) (31 mg, 43%). MS (ESI, pos. ion) m/z: 660.3 (M+1)

Workup

  1. customThe reaction mixture was degassed
  2. temperaturethe reaction was cooled to 23° C.
  3. filtrationfiltered through celite
  4. custompurified by silica gel chromatography (eluent: 0.5-10% MeOH/DCM)

Sources & evidence

ORD record
ord-4e8082409f264abcbb6f5988b29470a4
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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