1-Methyl-4-(prop-2-yn-1-yl)piperazine → N-(3-fluoro-4-(2-(3-(4-methylpiperazin-1-yl)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 1676301Notes

Reaction equation

HRID 1676301 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.[CH3:35][N:36]1[CH2:41][CH2:40][N:39]([CH2:42][C:43]#[CH:44])[CH2:38][CH2:37]1>>[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]([C:44]#[C:43][CH2:42][N:39]3[CH2:40][CH2:41][N:36]([CH3:35])[CH2:37][CH2:38]3)[S:17][C:10]=12

Participants

3

Reactant 2

HCID 135140911-Methyl-4-(prop-2-yn-1-yl)piperazineHCID 67347909N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Product 1

HCID 67347920N-(3-fluoro-4-(2-(3-(4-methylpiperazin-1-yl)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamideYield 70.8%

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-methyl-4-(prop-2-ynyl)piperazine (Example 17, Step A, 29.2 mg, 0.211 mmol) using the procedure described for Example 6, Step B. The crude was purified by preparative TLC (1 mm thickness, Rf=0.56), eluting with 10% MeOH (containing 7N NH3) in CHCl3. The product was obtained as a waxy solid (36 mg, 69%). HPLC: 100% purity (220 nm); LRMS (APCI+): 100% purity, 220 nm, m/z 602 (M+1) detected; 1H NMR (CDCl3, 400 MHz) δ 10.18 (s, 1H), 8.64 (s, 1H), 8.47 (d, J=5 Hz, 1H), 7.77 (m, 1H), 7.56 (s, 1H), 7.44 (m, 2H), 7.26 (m, 2H), 7.04 (m, 2H), 6.51 (d, J=5 Hz, 1H), 3.60 (s, 2H), 2.4-2.8 (m, 8H), 2.32 (s, 3H), 1.77 (m, 2H), 1.63 (m, 2H).

Workup

  1. customThe crude was purified by preparative TLC (1 mm thickness, Rf=0.56)
  2. washeluting with 10% MeOH (containing 7N NH3) in CHCl3

Sources & evidence

ORD record
ord-cb462a3841a7452f828b2088593f941b
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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