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Picolyl chloride → [5-(2-Methoxy-ethoxymethyl)-pyrrolo[2,1-f][1,2,4]triazin-4-yl]-(1-pyridin-2-ylmethyl-1H-indazol-5-yl)-amine

HRID 1072096
ノート
印刷プレビュー

反応式

HRID 1072096 の反応式
Cl[C:2]1[C:7]2=[C:8]([CH2:11][O:12][CH2:13][CH2:14][O:15][CH3:16])[CH:9]=[CH:10][N:6]2[N:5]=[CH:4][N:3]=1.C([O-])(O)=O.[Na+].[N:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[CH2:28][N:29]1[C:37]2[C:32](=[CH:33][C:34]([NH2:38])=[CH:35][CH:36]=2)[CH:31]=[N:30]1.FC1C=C(C=CC=1)CN1C2C(=CC(N)=CC=2)C=N1.N1C=CC=CC=1CCl>CC#N.C(Cl)Cl>[CH3:16][O:15][CH2:14][CH2:13][O:12][CH2:11][C:8]1[CH:9]=[CH:10][N:6]2[C:7]=1[C:2]([NH:38][C:34]1[CH:33]=[C:32]3[C:37](=[CH:36][CH:35]=1)[N:29]([CH2:28][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][N:22]=1)[N:30]=[CH:31]3)=[N:3][CH:4]=[N:5]2
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 5

HCID 23393Picolyl chlorideHCID 516892Sodium BicarbonateHCID 71470731-(3-Fluorobenzyl)-1H-indazol-5-amineHCID 219523661-(Pyridin-2-ylmethyl)-1H-indazol-5-amineHCID 223905494-Chloro-5-(2-methoxy-ethoxymethyl)-pyrrolo[2,1-f][1,2,4]triazine

生成物 1

HCID 22390521
[5-(2-Methoxy-ethoxymethyl)-pyrrolo[2,1-f][1,2,4]triazin-4-yl]-(1-pyridin-2-ylmethyl-1H-indazol-5-yl)-amine
収率 11%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒

実験手順

A suspension of 4-chloro-5-(2-methoxy-ethoxymethyl)-pyrrolo[2,1-f][1,2,4]triazine (24 mg, 0.099 mmole), NaHCO3 (42 mg, 5 equiv) and 1-pyridin-2-ylmethyl-1H-indazol-5-ylamine (22 mg, 1 equiv, prepared in the same manner as 1-(3-fluoro-benzyl)-1H-indazol-5-ylamine but using 2-picolyl chloride) in dry CH3CN (1 mL) was left stirring at RT for 1 hr. The reaction was diluted with DCM, washed with water and dried (Na2SO4). Removal of the solvent followed by radial chromatography (1 mm silica gel plate, gradient elution with DCM containing 0 to 1% MeOH) afforded the product as and oil (4.8 mg, 11%). 1H NMR (CDCl3) δ 3.26 (s, 3H), 3.76 (m, 4H), 4.90 (s, 2H), 5.75 (s, 2H), 6.56 (d, 1H, J=3 Hz), 6.83 (d, 1H, J=5 Hz), 7.18 (m, 1H), 7.40 (d, 1H, J=5 Hz), 7.49 (d, 1H, J=2 Hz), 7.56 (m, 2H), 7.96 (s, 1H), 8.07 (s, 1H), 8.22 (d, 1H, J=1 Hz), 8.59 (m, 1H), 9.65 (s, 1H); MS: 429 (M+H)+; HPLC Ret Time: 1.30 min (YMC ODS-A C18 S7, 3.0×50 mm, 2 min gradient (starting with 0% solvent B and ending with 70% solvent B), 5 mL/min.

後処理

  1. waitwas left
  2. washwashed with water
  3. dry with materialdried (Na2SO4)
  4. customRemoval of the solvent
  5. washfollowed by radial chromatography (1 mm silica gel plate, gradient elution with DCM containing 0 to 1% MeOH)

出典と根拠

ORDレコード
ord-a8cc4fe1bdd04c0dbadd08468fcfab26
出典データセット
uspto-grants-2005_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06908916B2

反応ノート

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