Potassium Carbonate → {(S)-1-[3-(2-Methoxy-pyridin-3-yl)-imidazo[1,2-b]pyridazin-6-yl]-pyrrolidin-3-yl}-methyl-carbamic acid isopropyl ester

HRID 870773ノート

反応式

HRID 870773 の反応式
[CH:1]([O:4][C:5](=[O:23])[N:6]([C@H:8]1[CH2:12][CH2:11][N:10]([C:13]2[CH:14]=[CH:15][C:16]3[N:17]([C:19](Br)=[CH:20][N:21]=3)[N:18]=2)[CH2:9]1)[CH3:7])([CH3:3])[CH3:2].[CH3:24][O:25][C:26]1[C:31](B(O)O)=[CH:30][CH:29]=[CH:28][N:27]=1.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>[CH:1]([O:4][C:5](=[O:23])[N:6]([C@H:8]1[CH2:12][CH2:11][N:10]([C:13]2[CH:14]=[CH:15][C:16]3[N:17]([C:19]([C:31]4[C:26]([O:25][CH3:24])=[N:27][CH:28]=[CH:29][CH:30]=4)=[CH:20][N:21]=3)[N:18]=2)[CH2:9]1)[CH3:7])([CH3:3])[CH3:2]

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 2762709(2-Methoxypyridin-3-yl)boronic acidHCID 86696483(S)-isopropyl (1-(3-bromoimidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-yl)(methyl)carbamate

生成物 1

HCID 71721711{(S)-1-[3-(2-Methoxy-pyridin-3-yl)-imidazo[1,2-b]pyridazin-6-yl]-pyrrolidin-3-yl}-methyl-carbamic acid isopropyl ester収率 87.4%

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
150 °C

実験手順

A mixture of [(S)-1-(3-bromo-imidazo[1,2-b]pyridazin-6-yl)-pyrrolidin-3-yl]-methyl-carbamic acid isopropyl ester (88 mg, 0.23 mmol), 2-methoxypyridine-3-boronic acid (46 mg, 0.3 mmol), K2CO3 (95 mg, 0.69 mmol) and dichlorobis(triphenylphosphine)palladium(II) (8.4 mg, 0.012 mmol) in MeCN/water (3.2 ml/0.8 ml) was heated in a microwave at 150° C. for 15 min. The water layer was removed and the organic layer was diluted with MeCN and filtered. The filtrate was subjected to preparative HPLC to give the titled compound (82.5 mg). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J=6.06 Hz, 6H) 2.13-2.32 (m, 2H) 2.89 (s, 3H) 3.43 (dd, J=10.48, 6.95 Hz, 1H) 3.48-3.56 (m, 1H) 3.69-3.76 (m, 2H) 4.09 (s, 3H) 4.99 (dt, J=12.38, 6.19 Hz, 2H) 6.62 (d, J=9.85 Hz, 1H) 7.04 (dd, J=7.45, 4.93 Hz, 1H) 7.79 (d, J=9.85 Hz, 1H) 8.13-8.19 (m, 2H) 8.86 (dd, J=7.71, 1.64 Hz, 1H). LRMS (ESI) m/z 411.2 [(M+H)]+, calc'd for C21H26N6O3: 410.48.

後処理

  1. customThe water layer was removed
  2. additionthe organic layer was diluted with MeCN
  3. filtrationfiltered

出典と根拠

ORDレコード
ord-ea4420a88f044e71a89789c5f110135d
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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