Sodium Bicarbonate → (2-methanesulfonyl-1-{2-[5-(4'-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

HRID 71792

반응식

HRID 71792 반응식
[CH3:1][O:2][C:3](=[O:40])[NH:4][CH:5]([C:13]([N:15]1[CH2:19][CH2:18][CH2:17][CH:16]1[C:20]1[NH:21][C:22]([C:25]2[CH:30]=[CH:29][C:28](B3OC(C)(C)C(C)(C)O3)=[CH:27][CH:26]=2)=[CH:23][N:24]=1)=[O:14])[C:6]([S:9]([CH3:12])(=[O:11])=[O:10])([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.[Na+]>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.COCCOC.O>[CH3:1][O:2][C:3](=[O:40])[NH:4][CH:5]([C:13]([N:15]1[CH2:19][CH2:18][CH2:17][CH:16]1[C:20]1[NH:21][C:22]([C:25]2[CH:30]=[CH:29][C:28]([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:27][CH:26]=2)=[CH:23][N:24]=1)=[O:14])[C:6]([S:9]([CH3:12])(=[O:10])=[O:11])([CH3:7])[CH3:8]

참가 물질

6

반응물 3

HCID 516892Sodium BicarbonateHCID 66620066[2-Methanesulfonyl-2-methyl-1-(2-{5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl esterHCID 66620141Methyl (1-(2-(4-(4-bromophenyl)-1H-imidazol-2-YL)pyrrolidin-1-YL)-3-methyl-1-oxobutan-2-YL)carbamate

생성물 1

HCID 66620509(2-methanesulfonyl-1-{2-[5-(4'-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester수율 15%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 18180031Water 1,2-dimethoxyethane용매

반응 조건

온도
80 °C

실험 절차

[2-Methanesulfonyl-2-methyl-1-(2-{5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester (700 mg, 1.22 mmol) and (1-{2-[5-(4-bromo-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (565 mg, 1.26 mmol) in 3:1 DME/H2O (15 mL) were treated with Pd(PPh3)4 (56 mg, 0.0050 mmol) and NaHCO3 (350 mg, 4.15 mmol). The mixture was stirred in a sealed tube at 80° C. for 24 hours. The mixture was filtered through a fritted glass funnel and concentrated. The mixture was subjected to a reverse phase HPLC column (5-95% MeCN—H2O; 0.1% TFA modifier) to afford (2-methanesulfonyl-1-{2-[5-(4′-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (150 mg, 15%) as a white solid (TFA salt): 1H NMR (CD3OD, 300 MHz) 7.85 (m, 10H), 5.25 (m, 2H), 4.24 (d, J=7.5 Hz, 1H), 4.13 (m, 2H), 3.88 (app d, J=7.5 Hz, 2H), 3.71 (s, 3H), 3.66 (s, 3H), 2.99 (s, 3H), 2.57 (m, 2H), 2.16 (m, 10H), 1.81 (s, 3H), 1.79 (s, 1H), 0.93 (m, 6H); MS (ESI) m/z 818 [M+H]+.

후처리

  1. filtrationThe mixture was filtered through a fritted glass funnel
  2. concentrationconcentrated

출처 및 근거

ORD 기록
ord-f92ba9642a2d4c3397e4fec30275d130
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822430B2

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