Potassium Carbonate → Isopropyl-carbamic acid 4-(6-butylamino-imidazo[1,2-b]pyridazin-3-yl)-benzyl ester

HRID 870701ノート

反応式

HRID 870701 の反応式
Br[C:2]1[N:6]2[N:7]=[C:8]([NH:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.CC1(C)C(C)(C)OB([C:24]2[CH:37]=[CH:36][C:27]([CH2:28][O:29][C:30](=[O:35])[NH:31][CH:32]([CH3:34])[CH3:33])=[CH:26][CH:25]=2)O1.C([O-])([O-])=O.[K+].[K+]>CC#N.O.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>[CH2:12]([NH:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([C:24]3[CH:37]=[CH:36][C:27]([CH2:28][O:29][C:30](=[O:35])[NH:31][CH:32]([CH3:33])[CH3:34])=[CH:26][CH:25]=3)=[CH:3][N:4]=2)[N:7]=1)[CH2:13][CH2:14][CH3:15]

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 866963223-Bromo-6-(butylamino)imidazo[1,2-b]pyridazineHCID 866964024-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl isopropylcarbamate

生成物 1

HCID 86696403Isopropyl-carbamic acid 4-(6-butylamino-imidazo[1,2-b]pyridazin-3-yl)-benzyl ester収率 138%

試薬・触媒・溶媒 2

HCID 178418476HCID 178418476、化合物触媒HCID 18373917Acetonitrile--water (1/1)溶媒

反応条件

温度
140 °C

実験手順

A mixture of (3-bromo-imidazo[1,2-b]pyridazin-6-yl)-butyl-amine (50 mg, 0.19 mmol), isopropyl-carbamic acid 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl ester (from part A, ˜0.5 mmol), K2CO3 (77 mg, 0.56 mmol) and dichlorobis(triphenylphosphine)palladium(II) (6.5 mg, 0.01 mmol) in MeCN/water (2 ml/0.5 ml) was heated in a microwave at 140° C. for 10 min. The reaction was repeated with another half of the bronic ester from Part A. The two reactions were combined for purification. The water layer was removed and the reaction mixture was diluted with MeCN (3 ml) and filtered. The filtrate was subjected to preparative HPLC to give the titled compound (100 mg). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.00 (t, J=7.39 Hz, 3H) 1.19 (d, J=6.62 Hz, 6H) 1.43-1.52 (m, 2H) 1.66-1.73 (m, 2H) 3.41 (td, J=7.06, 5.73 Hz, 2H) 3.87 (d, J=6.84 Hz, 1H) 4.49 (t, J=5.29 Hz, 1H) 5.14 (m, 1H) 6.45 (d, J=9.70 Hz, 1H) 7.46 (d, J=8.16 Hz, 2H) 7.66 (d, J=9.48 Hz, 1H) 7.81 (s, 1H) 8.14 (d, J=8.38 Hz, 2H). LRMS (ESI) m/z 382.2 [(M+H)]+, calc'd for C21H27N5O2: 381.48.

後処理

  1. customThe two reactions were combined for purification
  2. customThe water layer was removed
  3. additionthe reaction mixture was diluted with MeCN (3 ml)
  4. filtrationfiltered

出典と根拠

ORDレコード
ord-90593c318bb5400face4a1f918a8a648
出典データセット
uspto-grants-2015_03
特許番号
US08969565B2

反応ノート

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