Potassium Carbonate → HCID 118413234、化合物

HRID 929244ノート

反応式

HRID 929244 の反応式
CB(O)O.[N:5]1([C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[CH:20][C:19]([C:22]4[N:27]=[C:26]5[N:28]=[C:29]([O:31][C@H:32]6[C@H:36]7[O:37][CH2:38][C@@H:39]([OH:40])[C@H:35]7[O:34][CH2:33]6)[NH:30][C:25]5=[CH:24][C:23]=4Cl)=[CH:18][CH:17]=3)=[CH:12][CH:11]=2)[CH:9]=[N:8][CH:7]=[N:6]1.[C:42](=O)([O-])[O-].[K+].[K+]>[Pd+2].O1CCOCC1>[N:5]1([C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[CH:20][C:19]([C:22]4[N:27]=[C:26]5[N:28]=[C:29]([O:31][C@H:32]6[C@H:36]7[O:37][CH2:38][C@@H:39]([OH:40])[C@H:35]7[O:34][CH2:33]6)[NH:30][C:25]5=[CH:24][C:23]=4[CH3:42])=[CH:18][CH:17]=3)=[CH:12][CH:11]=2)[CH:9]=[N:8][CH:7]=[N:6]1

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 139377Methylboronic AcidHCID 60171877(3R,3aR,6R,6aR)-6-[[6-chloro-5-[4-[4-(1,2,4-triazol-1-yl)phenyl]phenyl]-1H-imidazo[4,5-b]pyridin-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol

生成物 1

HCID 118413234HCID 118413234、化合物

試薬・触媒・溶媒 2

HCID 105144Allyl(1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene)chloropalladium(II)触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
140 °C

実験手順

Methyl boronic acid (174 mg, 2.90 mmol), (3R,3aR,6R,6aR)-6-((5-(4′-(1H-1,2,4-triazol-1-yl)-[1,1′-biphenyl]-4-yl)-6-chloro-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol (150 mg, 0.290 mmol) and chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl)]palladium(II) (86 mg, 0.116 mmol) were added as solids to a microwave tube, followed by degassed 1,4-dioxane (2 mL) and 2 M aqueous potassium carbonate (1741 uL, 3.48 mmol). The tube was sealed and heated to 140° C. in a microwave for 30 minutes. The organic phase of the reaction was removed and evaporated under reduced pressure. The crude mixture was diluted in DMSO (2 mL) and purified by preparative HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column and eluting with a 5%-100% acetonitrile/water+0.05% TFA gradient followed by a 100% acetonitrile+0.05% TFA flush. The desired fractions were combined, evaporated under reduced pressure, and lyophilized from water/acetonitrile to give the title compound as white solid. LC-MS: calculated for C22H24N6O4 496.19 observed m/e: 497.24 (M+H)+ (Rt 0.79/2.5 min); 1H NMR δ (ppm) ((CD3)2SO):

後処理

  1. customThe tube was sealed
  2. customThe organic phase of the reaction was removed
  3. customevaporated under reduced pressure
  4. additionThe crude mixture was diluted in DMSO (2 mL)
  5. custompurified by preparative HPLC reverse phase (C-18)
  6. washeluting with a 5%-100% acetonitrile/water+0.05% TFA
  7. customflush
  8. customevaporated under reduced pressure

出典と根拠

ORDレコード
ord-12c5c21b0d884ea381a8a1c8e9901f98
出典データセット
uspto-grants-2016_03
特許番号
US09290517B2

反応ノート

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