Cesium carbonate → Methyl 6-(4-(dimethylamino)piperidin-1-yl)-1-isopropyl-1H-indazole-4-carboxylate

HRID 85448

反応式

HRID 85448 の反応式
Br[C:2]1[CH:3]=[C:4]([C:14]([O:16][CH3:17])=[O:15])[C:5]2[CH:6]=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.[CH3:18][N:19]([CH3:26])[CH:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>CO.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[CH3:18][N:19]([CH3:26])[CH:20]1[CH2:25][CH2:24][N:23]([C:2]2[CH:3]=[C:4]([C:14]([O:16][CH3:17])=[O:15])[C:5]3[CH:6]=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=3[CH:10]=2)[CH2:22][CH2:21]1

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 417391N,N-Dimethylpiperidin-4-amineHCID 634876Binap, (A+-)-HCID 67464993Methyl 6-bromo-1-isopropyl-1H-indazole-4-carboxylate

生成物 1

HCID 68210253Methyl 6-(4-(dimethylamino)piperidin-1-yl)-1-isopropyl-1H-indazole-4-carboxylate収率 25%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 887Methanol溶媒HCID 1140Toluene溶媒

反応条件

温度
115 °C

実験手順

To a 10-mL microwave tube were added methyl 6-bromo-1-(1-methylethyl)-1H-indazole-4-carboxylate (200 mg, 0.673 mmol), N,N-dimethyl-4-piperidinamine (95 mg, 0.740 mmol), toluene (3 mL), and cesium carbonate (329 mg, 1.010 mmol), and the mixture was degassed for 5 min by bubbling N2. BINAP (62.9 mg, 0.101 mmol) and Pd2(dba)3 (30.8 mg, 0.034 mmol) were added. The tube was sealed and the mixture was heated at 115° C. with stirring for 15 h. The mixture was diluted with methanol (5 mL) and filtered. The filtrate was concentrated and the residue was purified using reverse-phase HPLC to give 58 mg of product as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.45 (d, J=8.0 Hz, 6H), 1.54-1.61 (m, 2H), 1.87-1.96 (m, 2H), 2.31 (m, 6H), 2.80-2.83 (m, 2H), 3.83-3.86 (m, 2H), 3.93 (s, 3H), 4.98-5.04 (m, 1H), 7.29 (s, 1H), 7.57 (s, 1H), 8.17 (s, 1H). LCMS: (M+H)+=345.2

後処理

  1. customthe mixture was degassed for 5 min
  2. customby bubbling N2
  3. customThe tube was sealed
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated
  6. customthe residue was purified

出典と根拠

ORDレコード
ord-df772e9d080b431c90e0237028f1cfbd
出典データセット
uspto-grants-2014_09
特許番号
US08846935B2

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