Sodium Carbonate → tert-butyl 5-(4-((tert-butoxycarbonyl)(1-(tert-butoxycarbonyl)piperidin-4-yl)amino)phenyl)-3-(1-(3-fluorobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

HRID 531667Notes

Reaction equation

HRID 531667 reaction equation
[C:1]([O:5][C:6]([N:8]([CH:32]1[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH2:33]1)[C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[C:17]3[C:23](I)=[CH:22][N:21]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C:18]3=[N:19][CH:20]=2)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:45][C:46]1[CH:47]=[C:48]([CH:66]=[CH:67][CH:68]=1)[CH2:49][N:50]1[C:54]([CH3:55])=[C:53](B2OC(C)(C)C(C)(C)O2)[C:52]([CH3:65])=[N:51]1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.O.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]>[C:1]([O:5][C:6]([N:8]([CH:32]1[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH2:33]1)[C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[C:17]3[C:23]([C:53]4[C:52]([CH3:65])=[N:51][N:50]([CH2:49][C:48]5[CH:66]=[CH:67][CH:68]=[C:46]([F:45])[CH:47]=5)[C:54]=4[CH3:55])=[CH:22][N:21]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C:18]3=[N:19][CH:20]=2)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 900306711-(3-Fluoro-benzyl)-3,5-dimethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole2×HCID 90031137tert-butyl 5-(4-((tert-butoxycarbonyl)(1-(tert-butoxycarbonyl)piperidin-4-yl)amino)phenyl)-3-iodo-1H-pyrrolo[2,3-b]pyridine-1-carboxylate2×

Product 1

HCID 118523919tert-butyl 5-(4-((tert-butoxycarbonyl)(1-(tert-butoxycarbonyl)piperidin-4-yl)amino)phenyl)-3-(1-(3-fluorobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylateYield 25.3%

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-i of example-1, tert-butyl 5-(4-((tert-butoxycarbonyl)(1-(tert-butoxycarbonyl)piperidin-4-yl)amino)phenyl)-3-iodo-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (intermediate 66H) (150 mg, 0.20 mmol) was coupled with 1-(3-fluorobenzyl)-3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (intermediate 16) (89 mg, 0.27 mmol) using Pd(dppf)Cl2 (8 mg, 0.01 mmol) and sodium carbonate (63 mg, 0.6 mmol) in toluene/ethanol/water (20/10/5 ml) to afford 40 mg (25.3% yield) of the titled compound after column purification using 35% ethyl acetate in hexane as eluent. MS: m/z=694.9 (M-Boc+1).

Workup

  1. customreaction conditions

Sources & evidence

ORD record
ord-1d81ed83ba7e4137b3b581001fe206ba
Source dataset
uspto-grants-2016_05
Patent number
US09353107B2

Reaction notes

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