Potassium Carbonate → 6-(4-oxo-2-phenoxymethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl)-3',6'-dihydro-2'H-[2,4']bipyridinyl-1'-carboxylic acid tert-butyl ester

HRID 2046227ノート

反応式

HRID 2046227 の反応式
Br[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]3[N:14]=[C:15]([CH2:17][O:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH:16]=[C:10]3[C:9]2=[O:25])[CH:5]=[CH:4][CH:3]=1.B1([C:35]2[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH:36]=2)OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.CN(C=O)C.O.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:44]([O:43][C:41]([N:38]1[CH2:37][CH:36]=[C:35]([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]([N:8]3[CH2:13][CH2:12][N:11]4[N:14]=[C:15]([CH2:17][O:18][C:19]5[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=5)[CH:16]=[C:10]4[C:9]3=[O:25])[N:7]=2)[CH2:40][CH2:39]1)=[O:42])([CH3:47])([CH3:45])[CH3:46]

参加物

8

反応物 3

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 86670203HCID 86670203、化合物

生成物 1

HCID 574100246-(4-oxo-2-phenoxymethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl)-3',6'-dihydro-2'H-[2,4']bipyridinyl-1'-carboxylic acid tert-butyl ester収率 81.3%

試薬・触媒・溶媒 4

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
150 °C

実験手順

Tetrakis(triphenylphosphine)palladium(0) (7 mg, 0.006 mmol) was added to a stirred suspension of 5-(6-bromo-pyridin-2-yl)-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (50 mg, 0.125 mmol), (N-tert-butoxycarbonyl)-1,2,3,6-tetrahydropyridine-4-boronic acid pinacol ester (97 mg, 0.31 mmol) and potassium carbonate in a mixture of 1,4-dioxane (0.5 mL) and DMF (0.5 mL) in a sealed tube and under nitrogen. The mixture was stirred at 150° C. for 15 minutes under microwave irradiation. The mixture was diluted with water and extracted with AcOEt. The organic layer was separated, washed with brine, dried (MgSO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 100/0). The desired fractions were collected and the solvents evaporated in vacuo to yield 6-(4-oxo-2-phenoxymethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl)-3′,6′-dihydro-2′H-[2,4′]bipyridinyl-1′-carboxylic acid tert-butyl ester (51 mg, 81%) as a pale yellow solid.

後処理

  1. extractionextracted with AcOEt
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvents evaporated in vacuo
  7. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 100/0)
  8. customThe desired fractions were collected
  9. customthe solvents evaporated in vacuo

出典と根拠

ORDレコード
ord-757944ce232a4f4ea8053ba3f3a77b44
出典データセット
uspto-grants-2013_11
特許番号
US08592422B2

反応ノート

読み込み中…