5-Bromopyridine-2-carboxamide → HCID 59619817、化合物

HRID 445675

反応式

HRID 445675 の反応式
[CH:1]([N:4]1[CH:8]=[C:7]([N:9]2[C:21]3[C:20]4[CH:19]=[C:18](B5OC(C)(C)C(C)(C)O5)[CH:17]=[CH:16][C:15]=4[N:14]=[CH:13][C:12]=3[N:11]([CH3:31])[C:10]2=[O:32])[C:6]([CH3:33])=[N:5]1)([CH3:3])[CH3:2].Br[C:35]1[CH:36]=[CH:37][C:38]([C:41]([NH2:43])=[O:42])=[N:39][CH:40]=1>CN(C=O)C.C([O-])([O-])=O.[K+].[K+].CO.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:1]([N:4]1[CH:8]=[C:7]([N:9]2[C:21]3[C:20]4[CH:19]=[C:18]([C:35]5[CH:36]=[CH:37][C:38]([C:41]([NH2:43])=[O:42])=[N:39][CH:40]=5)[CH:17]=[CH:16][C:15]=4[N:14]=[CH:13][C:12]=3[N:11]([CH3:31])[C:10]2=[O:32])[C:6]([CH3:33])=[N:5]1)([CH3:3])[CH3:2]

参加物

7

反応物 2

HCID 7351515-Bromopyridine-2-carboxamideHCID 59619741HCID 59619741、化合物

生成物 1

HCID 59619817HCID 59619817、化合物

試薬・触媒・溶媒 4

HCID 887Methanol触媒HCID 178418476HCID 178418476、化合物触媒HCID 6228Dimethylformamide溶媒HCID 11430Potassium Carbonate溶媒

反応条件

温度
105 °C

実験手順

A mixture of 1-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-3-methyl-8-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,3-dihydro-imidazo[4,5-c]quinolin-2-one (Stage 112.1.1, 34 mg, 0.075 mmol), 5-bromo-pyridine-2-carboxylic acid amide (Combi-Blocks, San Diego, USA, 20 mg, 0.099 mmol), and PdCl2(PPh3)2 (3.5 mg, 0.005 mmol) in DMF (0.9 ml) and 1 M aqueous K2CO3 (0.187 ml) was stirred under argon at 105° C. for 2.5 h. The RM was cooled to rt. The mixture was diluted with MeOH+3 drops TFA and purified directly by Prep.HPLC (H2O (0.1% TFA)/CH3CN 97:3 to 55:45). The fractions containing product were collected together and basified with NaHCO3 (0.3 g), before being concentrated. The resulting layer was extracted with DCM, washed with brine, dried over Na2SO4, filtered and evaporated to dryness to give the title compound as a white solid. (HPLC: tR 2.44 min (Method A); M+H=442 MS-ES; 1H-NMR (d6-DMSO, 400 MHz) 9.00 (s, 1H), 8.75-8.69 (m, 1H), 8.24-8.19 (m, 1H), 8.18-8.07 (m, 2H), 8.07-7.98 (m, 3H), 7.75-7.67 (m, 1H), 7.61-7.56 (m, 1H), 4.61-4.48 (m, 1H), 3.58 (s, 3H), 1.97 (s, 3H), 1.45 (s, 3H), 1.43 (s, 3H))

後処理

  1. temperatureThe RM was cooled to rt
  2. custompurified directly by Prep.HPLC (H2O (0.1% TFA)/CH3CN 97:3 to 55:45)
  3. additionThe fractions containing product
  4. customwere collected together
  5. concentrationbefore being concentrated
  6. extractionThe resulting layer was extracted with DCM
  7. washwashed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customevaporated to dryness

出典と根拠

ORDレコード
ord-81d57a7faa5247fcaa029ae92de89cb6
出典データセット
uspto-grants-2013_07
特許番号
US08476294B2

関連ノート

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