Trifluoroacetic acid → 1-N'-[3-fluoro-4-[2-[5-[(2-methoxyethylamino)methyl]-2-pyridinyl]thieno[3,2-b]pyridin-7-yl]oxyphenyl]-1-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 1952471Notes

Reaction equation

HRID 1952471 reaction equation
[F:1][C:2]1[CH:36]=[C:35]([NH:37][C:38]([C:40]2([C:43](=[O:52])[NH:44]C3C=CC(F)=CC=3)[CH2:42][CH2:41]2)=[O:39])[CH:34]=[CH:33][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:14]3[N:19]=[CH:18][C:17]([CH2:20][N:21]([CH2:29][CH2:30][O:31][CH3:32])C(=O)OC(C)(C)C)=[CH:16][CH:15]=3)[S:13][C:6]=12.[C:53](O)([C:55]([F:58])(F)F)=O>ClCCl>[F:1][C:2]1[CH:36]=[C:35]([N:37]([C:2]2[CH:36]=[CH:53][C:55]([F:58])=[CH:33][CH:3]=2)[C:38]([C:40]2([C:43]([NH2:44])=[O:52])[CH2:41][CH2:42]2)=[O:39])[CH:34]=[CH:33][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:14]3[CH:15]=[CH:16][C:17]([CH2:20][NH:21][CH2:29][CH2:30][O:31][CH3:32])=[CH:18][N:19]=3)[S:13][C:6]=12

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57919567tert-Butyl (6-(7-(2-Fluoro-4-(1-(4-fluorophenylcarbamoyl)-cyclopropanecarboxamido)phenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl(2-methoxyethyl)carbamate

Product 1

HCID 665983951-N'-[3-fluoro-4-[2-[5-[(2-methoxyethylamino)methyl]-2-pyridinyl]thieno[3,2-b]pyridin-7-yl]oxyphenyl]-1-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamideYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To the compound 146 (0.59 g, 0.81 mmol) in dichloromethane (50 mL) was added TFA (3 mL). The solution was stirred for 18 h then concentrated. The residue was partitioned between dichloromethane and 1M NaOH, and filtered to remove insolubles. The organic phase was collected, washed with 1M NaOH, brine, dried (MgSO4), filtered, and concentrated to afford title compound 147 (0.35 g, 69% yield). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 10.40 (s, 1H), 10.01 (s, 1H), 8.55 (d, J=1.6 Hz, 1H), 8.51 (d, J=5.3 Hz, 1H), 8.31 (s, 1H), 8.22 (d, J=8.0 Hz, 1H), 7.92-7.87 (m, 2H), 7.65-7.61 (m, 2H), 7.52-7.43 (m, 2H), 7.17-7.12 (m, 2H), 6.64 (d, J=5.5 Hz, 1H), 3.77 (s, 2H), 3.40 (t, J=5.7 Hz, 2H), 3.23 (s, 3H), 2.64 (t, J=5.7 Hz, 2H), 1.46 (br s, 4H). MS (m/z): 630.1 (M+H).

Workup

  1. concentrationthen concentrated
  2. customThe residue was partitioned between dichloromethane and 1M NaOH
  3. filtrationfiltered
  4. customto remove insolubles
  5. customThe organic phase was collected
  6. washwashed with 1M NaOH, brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-57429766f377493986e47aa3e6184930
Source dataset
uspto-grants-2013_03
Patent number
US08404846B2

Reaction notes

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