Hydrochloric Acid → tert-Butyl (6-(7-(4-amino-3-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl(2-methoxyethyl)carbamate

HRID 84389

Reaction equation

HRID 84389 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[F:9].CC(C)([O-])C.[K+].Cl[C:17]1[CH:22]=[CH:21][N:20]=[C:19]2[CH:23]=[C:24]([C:26]3[N:31]=[CH:30][C:29]([CH2:32][N:33]([CH2:41][CH2:42][O:43][CH3:44])[C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[CH:28][CH:27]=3)[S:25][C:18]=12.Cl>CS(C)=O.O.C(Cl)Cl.CCOC(C)=O>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:17]2[CH:22]=[CH:21][N:20]=[C:19]3[CH:23]=[C:24]([C:26]4[N:31]=[CH:30][C:29]([CH2:32][N:33]([CH2:41][CH2:42][O:43][CH3:44])[C:34](=[O:40])[O:35][C:36]([CH3:37])([CH3:38])[CH3:39])=[CH:28][CH:27]=4)[S:25][C:18]=23)=[CH:4][C:3]=1[F:9]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 27359194-Amino-3-fluorophenolHCID 23665647Potassium tert-butoxideHCID 57919613tert-Butyl ((6-(7-chlorothieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)(2-methoxyethyl)carbamate

Product 1

HCID 57919486tert-Butyl (6-(7-(4-amino-3-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl(2-methoxyethyl)carbamateYield 32%

Reagents, catalysts & solvents 4

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4-amino-3-fluorophenol in DMSO (12 mL) was added potassium tert-butoxide (0.824 g, 7.34 mmol). After 30 min, intermediate 145 (2.451 g, 5.65 mmol) was added and the reaction mixture was heated at 100° C. for 1.5 h. It was then cooled down, poured in water (50 mL) at 40-45° C. and stirred for 30 min. EtOAc (40 mL), DCM (40 mL) and water (40 ml) were added and pH was adjusted to 7 by addition of HCl. Solids were removed by filtration through a paper filter and the two phases were separated. The organic layer was collected, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography, eluent DCM/MeOH:99/1, 98/2, 95/5, to afford intermediate 126a (0.952 g, 32% yield). MS (m/z): 525.2 (M+H).

Workup

  1. temperatureIt was then cooled down
  2. customSolids were removed by filtration through a paper
  3. filtrationfilter
  4. customthe two phases were separated
  5. customThe organic layer was collected
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash column chromatography, eluent DCM/MeOH

Sources & evidence

ORD record
ord-f88eb7732f534f82b50d70853c22e889
Source dataset
uspto-grants-2014_09
Patent number
US08846927B2

Linked notes

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