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

HRID 531553Notes

Reaction equation

HRID 531553 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.[CH3:40][C:41]1[C:45](B2OC(C)(C)C(C)(C)O2)=[C:44]([CH3:55])[N:43]([CH2:56][C:57]2[CH:58]=[C:59]([CH:62]=[CH:63][CH:64]=2)[C:60]#[N:61])[N:42]=1.C(=O)([O-])[O-].[Na+].[Na+]>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].C1(C)C=CC=CC=1.C(O)C.O>[C:60]([C:59]1[CH:58]=[C:57]([CH:64]=[CH:63][CH:62]=1)[CH2:56][N:43]1[C:44]([CH3:55])=[C:45]([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)[C:41]([CH3:40])=[N:42]1)#[N:61]

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 900312003-((3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)methyl)benzonitrile2×

Product 1

HCID 90031170tert-butyl 4-(4-(3-(1-(3-cyanobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)piperazine-1-carboxylateYield 36%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 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) (200 mg, 0.3 mmol) was coupled with 3-((3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)methyl)benzonitrile (intermediate 55) (103 mg, 0.3 mmol) in sodium carbonate (98 mg, 0.9 mmol), PdCl2(dppf) (11 mg, 0.01 mmol), toluene/ethanol/water (2/2/1 ml) to give 80 mg (36% yield) of titled compound. 1H NMR (CD3OD, 400 MHz): δ8.44-8.43 (d, 1H), 7.85-7.84 (d, 1H), 7.55-7.49 (m, 5H), 7.38 (s, 1H), 7.09-7.07 (d, 2H), 6.60 (s, 1H), 5.41 (s, 2H), 3.27-3.24 (m, 4H), 3.11-3.09 (m, 4H), 2.21-2.17 (m, 6H). MS: m/z=488.1 (M+1), HPLC—92.75% (method-B).

Workup

  1. customreaction conditions

Sources & evidence

ORD record
ord-146c8c22cda94bfa8dde87f788419a85
Source dataset
uspto-grants-2016_05
Patent number
US09353107B2

Reaction notes

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