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Potassium Phosphate, Tribasic → [1-(6-{5-[6-(4-{2-[5-(2-Methoxycarbonylamino-3-methyl-butyryl)-5-aza-spiro[2.4]hept-6-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-5-aza-spiro[2.4]heptane-5-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester

HRID 79983
ノート
印刷プレビュー

反応式

HRID 79983 の反応式
[CH3:1][O:2][C:3](=[O:30])[NH:4][CH:5]([C:9]([N:11]1[CH:17]([C:18]2[NH:19][C:20]([C:23]3[CH:28]=[CH:27][C:26](Br)=[CH:25][CH:24]=3)=[CH:21][N:22]=2)[CH2:16][C:13]2([CH2:15][CH2:14]2)[CH2:12]1)=[O:10])[CH:6]([CH3:8])[CH3:7].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].[CH3:54][O:55][C:56](=[O:87])[NH:57][CH:58]([C:62]([N:64]1[CH:70]([C:71]2[NH:72][C:73]([C:76]3[CH:85]=[CH:84][C:83]4[C:78](=[CH:79][CH:80]=[C:81](Br)[CH:82]=4)[CH:77]=3)=[CH:74][N:75]=2)[CH2:69][C:66]2([CH2:68][CH2:67]2)[CH2:65]1)=[O:63])[CH:59]([CH3:61])[CH3:60].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1>[CH3:54][O:55][C:56](=[O:87])[NH:57][CH:58]([C:62]([N:64]1[CH:70]([C:71]2[NH:72][C:73]([C:76]3[CH:85]=[CH:84][C:83]4[C:78](=[CH:79][CH:80]=[C:81]([C:26]5[CH:25]=[CH:24][C:23]([C:20]6[NH:19][C:18]([CH:17]7[CH2:16][C:13]8([CH2:14][CH2:15]8)[CH2:12][N:11]7[C:9](=[O:10])[CH:5]([NH:4][C:3]([O:2][CH3:1])=[O:30])[CH:6]([CH3:8])[CH3:7])=[N:22][CH:21]=6)=[CH:28][CH:27]=5)[CH:82]=4)[CH:77]=3)=[CH:74][N:75]=2)[CH2:69][C:66]2([CH2:68][CH2:67]2)[CH2:65]1)=[O:63])[CH:59]([CH3:61])[CH3:60]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 5

HCID 62657Potassium Phosphate, TribasicHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 66620752(1-{6-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-5-aza-spiro[2.4]heptane-5-carbonyl}-2-methyl-propyl)-carbamic acid methyl esterHCID 66620764(1-{6-[5-(6-Bromo-naphthalen-2-yl)-1H-imidazol-2-yl]-5-aza-spiro[2.4]heptane-5-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

生成物 1

HCID 66620650[1-(6-{5-[6-(4-{2-[5-(2-Methoxycarbonylamino-3-methyl-butyryl)-5-aza-spiro[2.4]hept-6-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-5-aza-spiro[2.4]heptane-5-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester収率 24%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
85 °C

実験手順

(1-{6-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-5-aza-spiro[2.4]heptane-5-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (0.10 g, 0.24 mmol), bis(pinacolato)diboron (0.073 g, 0.29 mmol), Palladium dichloride(dppf) (0.018 g, 0.024 mmol), and potassium acetate (0.071 g, 0.72 mmol) were suspended in 1,4-dioxane (1.2 mL) and degassed with argon for 30 minutes. The suspension was heated at 85° C. for 2 hours. The mixture was cooled, (1-{6-[5-(6-Bromo-naphthalen-2-yl)-1H-imidazol-2-yl]-5-aza-spiro[2.4]heptane-5-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (0.182 g, 0.346 mmol) and aqueous potassium phosphate (2M, 0.84 mL, 0.84 mmol) was added. The mixture was returned to heat for 16 hours at which time, Palladium(tetrakis)triphenylphosphine (0.014 g, 0.012 mmol) was added. The reaction was heated for an additional 4 hours. Upon completion, the crude reaction mixture was concentrated in vacuo and filtered through a Pd scavenging cartridge (Polymer Labs, PL-Guanidine MP SPE). The resulting slurry was diluted in DMF and purified by reverse phase HPLC (15-40% acetonitrile: water; 0.1% formic acid modifier), and lyophilized giving [1-(6-{5-[6-(4-{2-[5-(2-Methoxycarbonylamino-3-methyl-butyryl)-5-aza-spiro[2.4]hept-6-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-5-aza-spiro[2.4]heptane-5-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester (0.048 g, 24%) as a white solid.

後処理

  1. customdegassed with argon for 30 minutes
  2. temperatureThe mixture was cooled
  3. additionwas added
  4. temperatureThe reaction was heated for an additional 4 hours
  5. customUpon completion, the crude reaction mixture
  6. concentrationwas concentrated in vacuo
  7. filtrationfiltered through a Pd scavenging cartridge (Polymer Labs, PL-Guanidine MP SPE)
  8. additionThe resulting slurry was diluted in DMF
  9. custompurified by reverse phase HPLC (15-40% acetonitrile: water; 0.1% formic acid modifier)

出典と根拠

ORDレコード
ord-71583583fcf14a35b28231617f7f95a9
出典データセット
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08841278B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート