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

HRID 1261218Notes

Reaction equation

HRID 1261218 reaction equation
[F:1][C:2]1[CH:36]=[C:35]([N+:37]([O-])=O)[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]=[C:16]([CH:30]=[CH:31][CH:32]=3)[CH2:17][N:18]([CH2:26][CH2:27][O:28][CH3:29])[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[S:13][C:6]=12.[BH4-].[Na+].Cl>C1COCC1.CO.Cl[Ni]Cl>[NH2:37][C:35]1[CH:34]=[CH:33][C:3]([O:4][C:5]2[CH:10]=[CH:9][N:8]=[C:7]3[CH:11]=[C:12]([C:14]4[CH:15]=[C:16]([CH:30]=[CH:31][CH:32]=4)[CH2:17][N:18]([CH2:26][CH2:27][O:28][CH3:29])[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[S:13][C:6]=23)=[C:2]([F:1])[CH:36]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 59457707tert-Butyl 3-(7-(2-fluoro-4-nitrophenoxy)thieno{3,2-b}pyridine-2-yl)benzyl(2-methoxyethyl)carbamate

Product 1

HCID 59457715tert-Butyl 3-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)benzyl(2-methoxyethyl)carbamateYield 74.8%

Reagents, catalysts & solvents 3

HCID 24385Nickel DichlorideCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 73 (347 mg, 0.6 mmol) in THF (4 mL) and MeOH (2 mL), NiCl2 (372 mg, 1.6 mmol) was added and the solution was cooled to 0° C. NaBH4 (95 mg, 2.5 mmol) was added portion wise. After 20 minutes, the reaction was treated with 2 M HCl and solvents were removed under reduced pressure. The concentrated mixture was basified to pH 10 with ammonium hydroxide solution and the mixture was extracted with EtOAc, the extract was dried over anhydrous sodium sulfate, filtered and evaporated. The residue was purified by silica gel column chromatography, eluent EtOAc, to afford the title compound 74 (235 mg, 72% yield) as a white solid. 1H NMR (DMSO) δ (ppm): 8.47 (d, J=5.6 Hz, 1H), 7.97 (s, 1H), 7.77 (d, J=7.2 Hz, 1H), 7.70 (s, 1H), 7.48 (t, J=7.6 Hz, 1H), 6.56-6.51 (m, 2H), 6.44 (dd, J=6.3 Hz, 1H), 5.54 (s, 2H), 4.84 (s, 2H), 3.43 (s, 2H), 3.23 (s, 3H), 2.50 (q, J=2.2 Hz, 4H), 1.46-1.35 (m, 9H).

Workup

  1. customwere removed under reduced pressure
  2. extractionthe mixture was extracted with EtOAc
  3. dry with materialthe extract was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by silica gel column chromatography, eluent EtOAc

Sources & evidence

ORD record
ord-e5780a832a544837b2d25dc346614461
Source dataset
uspto-grants-2013_06
Patent number
US08470850B2

Reaction notes

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