m-Chloroperbenzoic acid → HCID 22055273, compound

HRID 1829932Notes

Reaction equation

HRID 1829932 reaction equation
ClC1C=CC=C(C(OO)=[O:9])C=1.[Cl:12][C:13]1[CH:14]=[C:15]([NH:28][C:29]2[C:34]3=[C:35]([CH2:38][S:39][CH2:40][CH2:41][OH:42])[CH:36]=[CH:37][N:33]3[N:32]=[CH:31][N:30]=2)[CH:16]=[CH:17][C:18]=1[O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=1>C(Cl)(Cl)Cl>[Cl:12][C:13]1[CH:14]=[C:15]([NH:28][C:29]2[C:34]3=[C:35]([CH2:38][S:39]([CH2:40][CH2:41][OH:42])=[O:9])[CH:36]=[CH:37][N:33]3[N:32]=[CH:31][N:30]=2)[CH:16]=[CH:17][C:18]=1[O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=1

Participants

4

Reactant 2

HCID 70297m-Chloroperbenzoic acidHCID 22055243HCID 22055243, compound

Product 1

HCID 22055273HCID 22055273, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

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. customthis was removed from the bath
  2. washwashed with a 6% aq. solution of NaHSO3, sat. aq. NaHCO3 (3×)
  3. dry with materialdried (Na2SO4)
  4. washRadial chromatography (silica gel plate eluted with DCM containing 0, 0.5, 1, 2, 3% MeOH)

Sources & evidence

ORD record
ord-ff036e68d03447f3b765b0e7ab9812fa
Source dataset
uspto-grants-2006_06
Patent number
US07064203B2

Reaction notes

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