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 1072096Notes

Reaction equation

HRID 1072096 reaction equation
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

Participants

8

Reactant 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

Product 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)-amineYield 11%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-a8cc4fe1bdd04c0dbadd08468fcfab26
Source dataset
uspto-grants-2005_06
Patent number
US06908916B2

Reaction notes

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