1-Ethyl-4-(prop-2-ynyl)piperazine → N-(4-(2-(3-(4-ethylpiperazin-1-yl)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 1676302Notes

Reaction equation

HRID 1676302 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:19]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[C:20]([C:22]2([C:25]([NH2:27])=[O:26])[CH2:24][CH2:23]2)=[O:21])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16](I)[S:17][C:10]=12.[CH2:35]([N:37]1[CH2:42][CH2:41][N:40]([CH2:43][C:44]#[CH:45])[CH2:39][CH2:38]1)[CH3:36]>>[CH2:35]([N:37]1[CH2:42][CH2:41][N:40]([CH2:43][C:44]#[C:45][C:16]2[S:17][C:10]3[C:11](=[N:12][CH:13]=[CH:14][C:9]=3[O:8][C:7]3[CH:6]=[CH:5][C:4]([N:19]([C:28]4[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=4)[C:20]([C:22]4([C:25]([NH2:27])=[O:26])[CH2:24][CH2:23]4)=[O:21])=[CH:3][C:2]=3[F:1])[CH:15]=2)[CH2:39][CH2:38]1)[CH3:36]

Participants

3

Reactant 2

HCID 211907411-Ethyl-4-(prop-2-ynyl)piperazineHCID 67347909N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Product 1

HCID 67348716N-(4-(2-(3-(4-ethylpiperazin-1-yl)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamideYield 10%

Procedure

Prepared from N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (Example 12, Step A, 50 mg, 0.0845 mmol) and 1-ethyl-4-(prop-2-ynyl)piperazine (Example 18, Step A, 32.2 mg, 0.211 mmol) using the procedure described for Example 6, Step B. The crude was purified by preparative TLC (1 mm thickness, Rf=0.67), eluting with 10% MeOH (containing 7N NH3) in CHCl3. The product was obtained as a waxy solid (5 mg, 10%). HPLC: 100% purity (220 nm); LRMS (APCI−): 100% purity, 220 nm, m/z 614 (M−1) detected; 1H NMR (400 MHz, CDCl3) δ 10.04 (s, 1H), 8.49 (d, J=5 Hz, 1H), 8.31 (br s, 1H), 7.75 (m, 1H), 7.58 (s, 1H), 7.43 (m, 2H), 7.24 (m, 2H), 7.06 (m, 2H), 6.52 (d, J=5 Hz, 1H), 3.64 (m, 2H), 3.61 (s, 2H), 2.4-2.8 (m, 8H), 1.80 (m, 2H), 1.62 (m, 2H), 1.12 (m, 3H).

Workup

  1. customThe crude was purified by preparative TLC (1 mm thickness, Rf=0.67)
  2. washeluting with 10% MeOH (containing 7N NH3) in CHCl3

Sources & evidence

ORD record
ord-64eff5c23d2f4c2db19c920a1e091bea
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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