Dabco → 4-(2-Fluoro-4-(3-(2-(4-fluorophenyl)acetyl)thioureido)phenoxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl pivalate

HRID 347464

Reaction equation

HRID 347464 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([NH:12][C:13](=[O:22])[CH2:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)=[S:11])[CH:5]=[CH:6][C:7]=1[OH:8].[C:23]([O:29][C:30]1[C:31]([CH3:40])=[C:32]2[N:37]([CH:38]=1)[N:36]=[CH:35][N:34]=[C:33]2Cl)(=[O:28])[C:24]([CH3:27])([CH3:26])[CH3:25].N12CCN(CC1)CC2>CC#N>[C:23]([O:29][C:30]1[C:31]([CH3:40])=[C:32]2[N:37]([CH:38]=1)[N:36]=[CH:35][N:34]=[C:33]2[O:8][C:7]1[CH:6]=[CH:5][C:4]([NH:9][C:10]([NH:12][C:13](=[O:22])[CH2:14][C:15]2[CH:16]=[CH:17][C:18]([F:21])=[CH:19][CH:20]=2)=[S:11])=[CH:3][C:2]=1[F:1])(=[O:28])[C:24]([CH3:27])([CH3:26])[CH3:25]

Participants

5

Reactant 3

HCID 9237DabcoHCID 210814951-(3-Fluoro-4-hydroxyphenyl)-3-(2-(4-fluorophenyl)acetyl)thiourea2×HCID 210816794-Chloro-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl 2,2-dimethylpropanoate2×

Product 1

HCID 115123454-(2-Fluoro-4-(3-(2-(4-fluorophenyl)acetyl)thioureido)phenoxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl pivalateYield 86.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a mixture of 1-(3-fluoro-4-hydroxyphenyl)-3-(2-(4-fluorophenyl)acetyl)thiourea (60 mg, 0.19 mmol, Compound A of Example 3), 4-chloro-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl pivalate (50 mg, 0.19 mmol, Compound D of Example 1) and 1,4-diazabicyclo[2.2.2]octane (DABCO, 21.3 mg, 0.19 mmol) was added MeCN (5 mL). The reaction was stirred at RT for 1 h and concentrated in vacuo. The residue was purified by flash chromatography (eluted with 1–15% MeOH/CH2Cl2) to give the title compound (91 mg, 86%) as a white solid. 1H NMR (CDCl3) δ 12.40 (s, 1H), 8.54 (s, 1H), 7.87 (m, 3H), 7.29 (m, 4H), 7.12 (m, 2H), 3.71 (s, 2H), 2.43 (s, 3H), 1.39 (s, 9H); MS(ESI+) m/z 554 (M+H) +.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was purified by flash chromatography (eluted with 1–15% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-cb5b9da66f71475282703b106bbb3c89
Source dataset
uspto-grants-2007_02
Patent number
US07173031B2

Linked notes

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