Nitrogen → HCID 22055243, compound

HRID 1829931Notes

Reaction equation

HRID 1829931 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:23]3=[C:24]([CH2:27][S:28][C:29](=O)[CH3:30])[CH:25]=[CH:26][N:22]3[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1.N#N.C[O-].[Na+].BrCC[OH:40]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:23]3=[C:24]([CH2:27][S:28][CH2:29][CH2:30][OH:40])[CH:25]=[CH:26][N:22]3[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1

Participants

6

Reactant 4

HCID 947NitrogenHCID 108982-BromoethanolHCID 10942334Sodium MethoxideHCID 86600483HCID 86600483, compound

Product 1

HCID 22055243HCID 22055243, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of thioacetic acid S-{4-[3-chloro-4-(3-fluoro-benzyloxy)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-5-ylmethyl}ester (80 mg, 0.175 mmole) in dry THF (4 mL) was sparged with N2 for 15 min. NaOMe (0.40 mL, 0.5 M in MeOH, 1.1 equiv), 2-bromoethanol (0.013 mL, 1 equiv) were added and the reaction was left stirring at RT. After 16 h, the solvents were removed and the residue was partitioned between DCM and water. The organic phase was separated, dried (Na2SO4), and the solvent removed. Radial chromatography (silica gel plate eluted with DCM containing 0, 0.5, 1, 2% MeOH) afforded 2-{4-[3-chloro-4-(3-fluoro-benzyloxy)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-5-ylmethylsulfanyl}-ethanol (35 mg, 44%): 1H NMR (CDCl3) δ 2.73 (t, 2H, J=5.9 Hz), 3.81 (t, 2H, J=5.9 Hz), 4.11 (s, 2H), 5.13 (s, 2H), 6.55 (d, 1H, J=2.6 Hz), 6.92–7.93 (m, 10H), 8.99 (s, 1H). Solid m-chloroperbenzoic acid (19 mg, 58 to 70%, 1 equiv) was added to an ice-cooled solution of the alcohol (35 mg, 0.18 mmole) in CHCl3 (4 mL). After 1 h, this was removed from the bath and washed with a 6% aq. solution of NaHSO3, sat. aq. NaHCO3 (3×) and then dried (Na2SO4). Radial chromatography (silica gel plate eluted with DCM containing 0, 0.5, 1, 2, 3% MeOH) afforded the title compound (22 mg, 60%): MS: 475 (M+H)+; HPLC Ret Time: 1.66 min (YMC Xterra C18 S7, 3.0×50 mm column, 2 min gradient, 5 mL/min).

Workup

  1. waitthe reaction was left
  2. customthe solvents were removed
  3. customthe residue was partitioned between DCM and water
  4. customThe organic phase was separated
  5. dry with materialdried (Na2SO4)
  6. customthe solvent removed
  7. washRadial chromatography (silica gel plate eluted with DCM containing 0, 0.5, 1, 2% MeOH)

Sources & evidence

ORD record
ord-e7786e527001421eb08a72d384dd54d6
Source dataset
uspto-grants-2006_06
Patent number
US07064203B2

Reaction notes

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