Potassium Carbonate → 4-Cyano-2-{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}-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1185884ノート

反応式

HRID 1185884 の反応式
[CH3:1][O:2][C:3](=[O:38])[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](B4OC(C)(C)C(C)(C)O4)=[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].[C:39]([O:43][C:44]([N:46]1[CH2:50][CH:49]([C:51]#[N:52])[CH2:48][CH:47]1[C:53]1[NH:54][C:55]([C:58]2[CH:67]=[CH:66][C:65]3[C:60](=[CH:61][CH:62]=[C:63](Br)[CH:64]=3)[CH:59]=2)=[CH:56][N:57]=1)=[O:45])([CH3:42])([CH3:41])[CH3:40].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>[C:39]([O:43][C:44]([N:46]1[CH2:50][CH:49]([C:51]#[N:52])[CH2:48][CH:47]1[C:53]1[NH:54][C:55]([C:58]2[CH:67]=[CH:66][C:65]3[C:60](=[CH:61][CH:62]=[C:63]([C:26]4[CH:25]=[CH:24][C:23]([C:20]5[NH:19][C:18]([CH:17]6[CH2:16][C:13]7([CH2:14][CH2:15]7)[CH2:12][N:11]6[C:9](=[O:10])[CH:5]([NH:4][C:3]([O:2][CH3:1])=[O:38])[CH:6]([CH3:8])[CH3:7])=[N:22][CH:21]=5)=[CH:28][CH:27]=4)[CH:64]=3)[CH:59]=2)=[CH:56][N:57]=1)=[O:45])([CH3:42])([CH3:41])[CH3:40]

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 66620446[2-Methyl-1-(6-{5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-5-aza-spiro[2.4]heptane-5-carbonyl)-propyl]-carbamic acid methyl esterHCID 666210142-[5-(6-Bromo-naphthalen-2-yl)-1H-imidazol-2-yl]-4-cyano-pyrrolidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 666211324-Cyano-2-{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}-pyrrolidine-1-carboxylic acid tert-butyl ester収率 51%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 80711,2-Dimethoxyethane溶媒

実験手順

[2-Methyl-1-(6-{5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-5-aza-spiro[2.4]heptane-5-carbonyl)-propyl]-carbamic acid methyl ester (997 mg, 1.91 mmol), 2-[5-(6-Bromo-naphthalen-2-yl)-1H-imidazol-2-yl]-4-cyano-pyrrolidine-1-carboxylic acid tert-butyl ester, Pd(PPh3)4 (184 mg, 0.159 mmol), and K2CO3 (2 M in H2O, 1.9 mL, 3.8 mmol) were combined in 1,2-dimethoxyethane (16 mL). The reaction mixture was degassed with bubbling N2 for 10 minutes then heated to reflux for 3.5 h. After heating, the reaction mixture was cooled to RT, diluted with EtOAc and washed with H2O and brine. The organic phase was dried over MgSO4, then filtered and concentrated. The resulting residue was purified with silica column chromatography 0% to 100% (10% MeOH/DCM)/EtOAc to afford the title compound (641 mg, 51%).

後処理

  1. customThe reaction mixture was degassed with bubbling N2 for 10 minutes
  2. temperaturethen heated
  3. temperatureto reflux for 3.5 h
  4. temperatureAfter heating
  5. additiondiluted with EtOAc
  6. washwashed with H2O and brine
  7. dry with materialThe organic phase was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was purified with silica column chromatography 0% to 100% (10% MeOH/DCM)/EtOAc

出典と根拠

ORDレコード
ord-65b7ff36878f405fac67a7ea85772d71
出典データセット
uspto-grants-2014_03
特許番号
US08669234B2

反応ノート

読み込み中…