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

HRID 531546Notes

Reaction equation

HRID 531546 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:11]3[CH:16]=[CH:15][C:14]([N:17]4[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]4)=[CH:13][CH:12]=3)[CH:9]=2)[N:4]([S:30]([C:33]2[CH:39]=[CH:38][C:36]([CH3:37])=[CH:35][CH:34]=2)(=[O:32])=[O:31])[CH:3]=1.[F:40][C:41]1[CH:42]=[C:43]([CH:60]=[CH:61][CH:62]=1)[CH2:44][N:45]1[CH:49]=[C:48](C2OC(C)(C)C(C)(C)O2)[C:47](C)=[N:46]1.[C:63](=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1(C)C=CC=CC=1.C(O)C.O>[F:40][C:41]1[CH:42]=[C:43]([CH:60]=[CH:61][CH:62]=1)[CH2:44][N:45]1[C:49]([CH3:63])=[C:48]([C:2]2[C:10]3[C:5](=[N:6][CH:7]=[C:8]([C:11]4[CH:16]=[CH:15][C:14]([N:17]5[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]5)=[CH:13][CH:12]=4)[CH:9]=3)[N:4]([S:30]([C:33]3[CH:39]=[CH:38][C:36]([CH3:37])=[CH:35][CH:34]=3)(=[O:32])=[O:31])[CH:3]=2)[CH:47]=[N:46]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 90030611tert-butyl 4-(4-(3-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)piperazine-1-carboxylate2×HCID 900308431-(3-fluorobenzyl)-3-methyl-4-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)-1H-pyrazole2×

Product 1

HCID 90030894tert-butyl 4-(4-(3-(1-(3-fluorobenzyl)-5-methyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)piperazine-1-carboxylateYield 76.2%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 86587398Ethanol toluene waterSolvent

Procedure

Using similar reaction conditions as described in step-ii of example-1, tert-butyl 4-(4-(3-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)piperazine-1-carboxylate (intermediate 41) (300 mg, 0.455 mmol) was coupled with 1-(3-fluorobenzyl)-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (intermediate 12) (187 mg, 0.592 mmol) in sodium carbonate (145 mg, 1.365 mmol), Pd(PPh3)2Cl2 (16 mg, 0.0227 mmol), Toluene/ethanol/water (5/10/1 ml) to give 250 mg (76.2% yield) of titled compound after purification by column (SiO2) using 20% ethyl acetate in hexane as eluent. 1H NMR (CDCl3, 300 MHz): δ 8.64 (s, 1H), 8.12-8.09 (d, 2H), 7.87 (s, 1H), 7.70 (s, 1H), 7.56 (s, 1H), 7.49-7.44 (m, 2H), 7.34-7.25 (m, 2H), 7.01-6.99 (m, 3H), 5.31 (s, 2H), 3.62-3.60 (t, 4H), 3.25-3.19 (t, 4H), 2.39 (s, 3H), 2.37 (s, 3H), 1.49 (s, 9H). MS: m/z=721.1 (M+1).

Workup

  1. customreaction conditions

Sources & evidence

ORD record
ord-67a39d12da9b49339dd7e74ff3e9dbf2
Source dataset
uspto-grants-2016_05
Patent number
US09353107B2

Reaction notes

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