2-Methoxyethylamine → N-(3-Fluoro-4-(2-(5-((2-methoxyethylamino)methyl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N-phenylcyclopropane-1,1-dicarboxamide

HRID 84385Notes

Reaction equation

HRID 84385 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:26]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C:27]([C:29]2([C:32]([NH2:34])=[O:33])[CH2:31][CH2:30]2)=[O:28])[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:18]3[CH:23]=[CH:22][C:21]([CH:24]=O)=[CH:20][N:19]=3)[S:17][C:10]=12.[CH3:41][O:42][CH2:43][CH2:44][NH2:45].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([N:26]([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:27]([C:29]2([C:32]([NH2:34])=[O:33])[CH2:31][CH2:30]2)=[O:28])[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:18]3[CH:23]=[CH:22][C:21]([CH2:24][NH:45][CH2:44][CH2:43][O:42][CH3:41])=[CH:20][N:19]=3)[S:17][C:10]=12

Participants

5

Reactant 3

HCID 80182-Methoxyethylamine2×HCID 5049666Sodium triacetoxyborohydride2×HCID 86635186N-(3-Fluoro-4-(2-(5-formylpyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N-phenylcyclopropane-1,1-dicarboxamide

Product 1

HCID 66598605N-(3-Fluoro-4-(2-(5-((2-methoxyethylamino)methyl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N-phenylcyclopropane-1,1-dicarboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Aldehyde 141 (0.20 g, 0.362 mmol) and 2-methoxyethylamine (0.158 mL, 1.810 mmol) were dissolved in THF (50 mL) to give a colorless solution. Sodium trisacetoxyborohydride (0.384 g, 1.810 mmol) was added and the mixture was stirred at r.t. for 20 h. Additional 2-methoxyethylamine (0.158 mL, 1.810 mmol) and sodium trisacetoxyborohydride (0.384 g, 1.810 mmol) were added, and the mixture was stirred for a further 20 h. It was then concentrated, partitioned between water and dichloromethane. Organic phase was collected, washed with H2O, 1M NaOH, and brine, dried (MgSO4), filtered and concentrated. The residue was purified by Gilson Reverse Phase HPLC (Aquasil C18, 40-90% MeOH/water, 30 min, elutes ˜20 min) and lyophilized, to afford title compound 142. Starting material (50 mg) was also isolated.

Workup

  1. customto give a colorless solution
  2. stirringthe mixture was stirred for a further 20 h
  3. concentrationIt was then concentrated
  4. custompartitioned between water and dichloromethane
  5. customOrganic phase was collected
  6. washwashed with H2O, 1M NaOH, and brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by Gilson Reverse Phase HPLC (Aquasil C18, 40-90% MeOH/water, 30 min, elutes ˜20 min)

Sources & evidence

ORD record
ord-70fd5e914395454f8c695a314a8d9333
Source dataset
uspto-grants-2014_09
Patent number
US08846927B2

Reaction notes

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