Potassium Carbonate → HCID 66621493, compound

HRID 71856Notes

Reaction equation

HRID 71856 reaction equation
[CH3:1][O:2][C:3](=[O:40])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16](=[O:39])[NH:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:29]=[CH:28][C:27](B3OC(C)(C)C(C)(C)O3)=[CH:26][CH:25]=2)=[CH:20][CH:19]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].[CH3:41][O:42][C:43](=[O:68])[NH:44][CH:45]([C:49]([N:51]1[CH2:55][CH2:54][CH2:53][CH:52]1[C:56]1[NH:57][C:58]([C:61]2[CH:66]=[CH:65][C:64](Br)=[CH:63][CH:62]=2)=[CH:59][N:60]=1)=[O:50])[CH:46]([CH3:48])[CH3:47].C(=O)([O-])[O-].[K+].[K+]>COCCOC.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>[CH3:1][O:2][C:3](=[O:40])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16](=[O:39])[NH:17][C:18]1[CH:19]=[CH:20][C:21]([C:24]2[CH:25]=[CH:26][C:27]([C:64]3[CH:65]=[CH:66][C:61]([C:58]4[NH:57][C:56]([CH:52]5[CH2:53][CH2:54][CH2:55][N:51]5[C:49](=[O:50])[CH:45]([NH:44][C:43]([O:42][CH3:41])=[O:68])[CH:46]([CH3:48])[CH3:47])=[N:60][CH:59]=4)=[CH:62][CH:63]=3)=[CH:28][CH:29]=2)=[CH:22][CH:23]=1)=[O:10])[CH:6]([CH3:8])[CH3:7]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 66620141Methyl (1-(2-(4-(4-bromophenyl)-1H-imidazol-2-YL)pyrrolidin-1-YL)-3-methyl-1-oxobutan-2-YL)carbamateHCID 66621418(2-Methyl-1-{2-[4'-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-biphenyl-4-ylcarbamoyl]-pyrrolidine-1-carbonyl}-propyl)-carbamic acid methyl ester

Product 1

HCID 66621493HCID 66621493, compoundYield 27.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

(2-Methyl-1-{2-[4′-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-biphenyl-4-ylcarbamoyl]-pyrrolidine-1-carbonyl}-propyl)-carbamic acid methyl ester (102 mg, 0.227 mmol), (1-{2-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (125 mg, 0.227 mmol), Pd(PPh3)4 (13 mg, 0.0114 mmol) and a 2 M aqueous solution of potassium carbonate (0.227 mL, 0.454 mmol) were degassed in 1,2-dimethoxyethane (2 mL) for 15 min. The stirred suspension was heated to 85° C. for 4 hours then concentrated, brought up in DMF/water and purified by reverse phase preparative HPLC to provide {1-[2-(4″-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-[1,1′;4′,1″]terphenyl-4-ylcarbamoyl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (49 mg, 27%). (DMSO-d6, 400 MHz) 11.78 (s, 1H), 10.14 (s, 1H), 7.82-7.67 (m, 11H), 7.52 (d, J=1.8 Hz, 1H), 7.34-7.28 (m, 2H), 5.08 (m, 1H), 4.49 (m, 1H), 4.05 (m, 2H), 3.81 (m, 3H), 3.64 (m, 1H), 3.54 (s, 3H), 3.53 (s, 3H), 2.17-1.88 (m, 10H), 0.97-0.85 (m, 12H); MS (ESI) m/z 792 [M+H]+.

Workup

  1. concentrationthen concentrated
  2. custompurified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-ffd68bbd1d7c4ddcad1cd9fcf5ab6b1e
Source dataset
uspto-grants-2014_09
Patent number
US08822430B2

Reaction notes

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