HCID 22354399, compound → N-(3-fluoro-4-(2-(3-methyl-3-(4-methylpiperazin-1-yl)but-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 1676310Notes

Reaction equation

HRID 1676310 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]([C:42]([CH3:46])([C:44]#[CH:45])[CH3:43])[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:45]#[C:44][C:42]([CH3:46])([N:39]3[CH2:38][CH2:37][N:36]([CH3:35])[CH2:41][CH2:40]3)[CH3:43])[S:17][C:10]=12

Participants

3

Reactant 2

HCID 22354399HCID 22354399, compoundHCID 67347909N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Product 1

HCID 67349022N-(3-fluoro-4-(2-(3-methyl-3-(4-methylpiperazin-1-yl)but-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamideYield 18.8%

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, 20 mg, 0.0338 mmol) and 1-methyl-4-(2-methylbut-3-yn-2-yl)piperazine (11.2 mg, 0.0676 mmol) using the procedure described for Example 6, Step B. The crude was purified by preparative TLC (1 mm thickness, Rf=0.16) eluting with 10% MeOH/DCM. The compound was re-purified by preparative TLC (0.5 mm thickness, Rf=0.84) eluting with 15% MeOH (containing 7N NH3) in CHCl3, to obtain product of adequate purity. The product was obtained as a beige powder (4 mg, 18%). HPLC: 95% purity (220 nm); LCMS (APCI−): 100% purity, 220 nm, m/z 629 (M−1) detected; 1H NMR (400 MHz, CDCl3) δ 9.95 (s, 1H), 8.49 (d, J=5 Hz, 1H), 8.40 (br s, 1H), 7.73 (m, 1H), 7.54 (s, 1H), 7.44 (m, 2H), 7.21 (m, 2H), 7.06 (t, J=9 Hz, 2H), 6.54 (d, J=5 Hz, 1H), 2.84 (m, 4H), 2.65 (m, 4H), 2.39 (s, 3H), 1.82 (m, 2H), 1.64 (m, 2H), 1.51 (s, 6H).

Workup

  1. customThe crude was purified by preparative TLC (1 mm thickness, Rf=0.16)
  2. washeluting with 10% MeOH/DCM
  3. customThe compound was re-purified by preparative TLC (0.5 mm thickness, Rf=0.84)
  4. washeluting with 15% MeOH (containing 7N NH3) in CHCl3
  5. customto obtain product of adequate purity

Sources & evidence

ORD record
ord-7a10195dcc6149b1bf396a40708414d9
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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