Sodium Carbonate → tert-butyl 4-(4-(3-(1-(3,5-difluorobenzyl)-1H-pyrazol-3-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-(methylsulfonamido)phenyl)piperazine-1-carboxylate

HRID 531698Notes

Reaction equation

HRID 531698 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:15]=[CH:14][N:13]([CH2:16][C:17]4[CH:22]=[C:21]([F:23])[CH:20]=[C:19]([F:24])[CH:18]=4)[N:12]=3)=[CH:9][N:8]([S:25]([C:28]3[CH:34]=[CH:33][C:31]([CH3:32])=[CH:30][CH:29]=3)(=[O:27])=[O:26])[C:5]2=[N:6][CH:7]=1.[CH3:35][S:36]([NH:39][C:40]1[CH:45]=[C:44](B2OC(C)(C)C(C)(C)O2)[CH:43]=[CH:42][C:41]=1[N:55]1[CH2:60][CH2:59][N:58]([C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[CH2:57][CH2:56]1)(=[O:38])=[O:37].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.O.C(OCC)(=O)C.CCCCCC.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:23][C:21]1[CH:22]=[C:17]([CH:18]=[C:19]([F:24])[CH:20]=1)[CH2:16][N:13]1[CH:14]=[CH:15][C:11]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([C:44]4[CH:43]=[CH:42][C:41]([N:55]5[CH2:56][CH2:57][N:58]([C:61]([O:63][C:64]([CH3:65])([CH3:66])[CH3:67])=[O:62])[CH2:59][CH2:60]5)=[C:40]([NH:39][S:36]([CH3:35])(=[O:37])=[O:38])[CH:45]=4)[CH:3]=3)[N:8]([S:25]([C:28]3[CH:29]=[CH:30][C:31]([CH3:32])=[CH:33][CH:34]=3)(=[O:26])=[O:27])[CH:9]=2)=[N:12]1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 90022155Tert-butyl 4-(2-(methylsulfonamido)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine-1-carboxylate2×HCID 900648145-bromo-3-(1-(3,5-difluorobenzyl)-1H-pyrazol-3-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine2×

Product 1

HCID 118524029tert-butyl 4-(4-(3-(1-(3,5-difluorobenzyl)-1H-pyrazol-3-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-(methylsulfonamido)phenyl)piperazine-1-carboxylateYield 39.9%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolventHCID 86587398Ethanol toluene waterSolvent

Procedure

Using similar reaction conditions as described in step-ii of example-1, 5-bromo-3-(1-(3,5-difluorobenzyl)-1H-pyrazol-3-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine (intermediate 63) (100 mg, 0.184 mmol) was coupled with tert-butyl 4-(2-(methylsulfonamido)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine-1-carboxylate (intermediate 69G) (106 mg, 0.22 mmol) using sodium carbonate (58 mg, 0.552 mmol) and Pd(PPh3)4 (10 mg, 0.009 mmol) in toluene/ethanol/water (2/2/1 ml). This afforded 60 mg (39.9% yield) after preparative TLC (Silicagel-1000 micron) using 40% ethyl acetate in hexane as eluent. MS: m/z=818.6 (M+1).

Workup

  1. customreaction conditions

Sources & evidence

ORD record
ord-049ad1131e6b4facaa12c9ea54e3e6fb
Source dataset
uspto-grants-2016_05
Patent number
US09353107B2

Reaction notes

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