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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
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HRID 1072096 반응식
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
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참가 물질

8

반응물 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

생성물 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
수율 11%

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-a8cc4fe1bdd04c0dbadd08468fcfab26
출처 데이터셋
uspto-grants-2005_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06908916B2

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