Triethylamine → HCID 67411874, compound

HRID 1072082Notes

Reaction equation

HRID 1072082 reaction equation
[C:1]([O:4][CH2:5][C:6](Cl)=[O:7])(=[O:3])[CH3:2].[NH2:9][CH:10]1[CH2:15][CH2:14][N:13]([CH2:16][C:17]2[CH:18]=[CH:19][N:20]3[C:25]=2[C:24]([NH:26][C:27]2[CH:28]=[C:29]4[C:33](=[CH:34][CH:35]=2)[N:32]([CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([F:43])[CH:38]=2)[N:31]=[CH:30]4)=[N:23][CH:22]=[N:21]3)[CH2:12][CH2:11]1.C(N(CC)CC)C>C(Cl)Cl>[F:43][C:39]1[CH:38]=[C:37]([CH:42]=[CH:41][CH:40]=1)[CH2:36][N:32]1[C:33]2[C:29](=[CH:28][C:27]([NH:26][C:24]3[C:25]4=[C:17]([CH2:16][N:13]5[CH2:12][CH2:11][CH:10]([NH:9][C:6]([CH2:5][O:4][C:1](=[O:3])[CH3:2])=[O:7])[CH2:15][CH2:14]5)[CH:18]=[CH:19][N:20]4[N:21]=[CH:22][N:23]=3)=[CH:35][CH:34]=2)[CH:30]=[N:31]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 26297Acetoxyacetyl chlorideHCID 10151881HCID 10151881, compound

Product 1

HCID 67411874HCID 67411874, compoundYield 127.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Acetoxyacetyl chloride (46 mg, 2 equiv) was added dropwise to a solution of [5-(4-amino-piperidin-1-ylmethyl)-pyrrolo[2,1-f][1,2,4]triazin-4-yl]-[1-(3-fluoro-benzyl)-1H-indazol-5-yl]-amine (47 mg, 0.1 mmole) (80 mg, 0.17 mmole) and triethylamine (71 μL, 3 equiv.) in dry DCM (3 mL) at 0° C. under nitrogen. After stirring at 0° C. for 3 hr and at RT for 1 hr, it was diluted with DCM, washed with water and dried (Na2SO4). Removal of the solvent followed by radial chromatography (2 mm silica gel plate, gradient elution with DCM containing 0 to 2% MeOH) afforded acetic acid (1-{4-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-pyrrolo[2,1-f][1,2,4]triazin-5-ylmethyl}-piperidin-4-ylcarbamoyl)-methyl ester as a solid (73 mg, 75%). A solution of this ester in THF (0.4 mL) was treated with aq. NaOH (IN, 0.38 mL, 3 equiv.). After 2 hr at RT it was diluted with DCM, washed with water and dried (Na2SO4). Removal of the solvent followed by radial chromatography (2 mm silica gel plate employing gradient elution with DCM containing 0 to 3% MeOH) afforded the title compound as a solid (47 mg, 70%). MS: 529 (M+H)+; HPLC Ret Time: 1.37 min (YMC Xterra ODS S7 3.0×50 mm column, 2 min gradient, 5 ml/min).

Workup

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

Sources & evidence

ORD record
ord-b0d2d8279ade49bdbd76dc7f0f5a8511
Source dataset
uspto-grants-2005_06
Patent number
US06908916B2

Reaction notes

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