Propargyl bromide → 1-[3-({4-Amino-7-[3-(1-piperidinyl)-1-propyn-1-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl}carbonyl)phenyl]-3-(2,4-dichlorophenyl)urea

HRID 2108357Notes

Reaction equation

[NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:7](Br)[C:8]#[CH:9].[NH2:11][C:12]1[C:17]2=[C:18]([C:22]([C:24]3[CH:25]=[C:26]([NH:30][C:31]([NH:33][C:34]4[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][C:35]=4[Cl:41])=[O:32])[CH:27]=[CH:28][CH:29]=3)=[O:23])[CH:19]=[C:20](Br)[N:16]2[N:15]=[CH:14][N:13]=1>[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:11][C:12]1[C:17]2=[C:18]([C:22]([C:24]3[CH:25]=[C:26]([NH:30][C:31]([NH:33][C:34]4[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][C:35]=4[Cl:41])=[O:32])[CH:27]=[CH:28][CH:29]=3)=[O:23])[CH:19]=[C:20]([C:7]#[C:8][CH2:9][N:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)[N:16]2[N:15]=[CH:14][N:13]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of piperidine (2 mL) and propargyl bromide (80 wt % in toluene, 0.02 mL, 0.19 mmol) was purged with argon for 10 minutes. The solution was treated with 95G (20 mg, 0.04 mmol), CuI (1 mg, 0.008 mmol) and PdCl2(PPh3)2 (3 mg, 0.004 mmol). The reaction mixture was heated to 80° C. for one hour and then concentrated. The residue was purified by flash chromatography (SiO2, 0% to 10% MeOH/CH2Cl2) to afford the desired compound (13 mg, 62%). HPLC tR=3.17 min (Chromolith SpeedROD 4.6×50 mm, 10-90% aqueous methanol containing 0.1% TFA, 4 min gradient, monitored at 254 nm). [M+H+]=562.27.

Workup

concentrationconcentrated
customThe residue was purified by flash chromatography (SiO2, 0% to 10% MeOH/CH2Cl2)

Sources & evidence

ORD record: ord-f37761a994be495cbe329a85c46e07cd
Source dataset: uspto-grants-2009_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07514435B2

Reaction notes

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