Nitrogen → (5-{2-[(3',4',5'-Trihydroxy-biphenyl-2-carbonyl)-amino]-phenyl}-thiophen-2-yl)-acetic acid

HRID 383614Notes

Reaction equation

HRID 383614 reaction equation
N#N.C[O:4][C:5]1[CH:6]=[C:7]([C:15]2[C:16]([C:21]([NH:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:30]3[S:34][C:33]([CH2:35][C:36]([OH:38])=[O:37])=[CH:32][CH:31]=3)=[O:22])=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:8]=[C:9]([O:13]C)[C:10]=1[O:11]C.B(Br)(Br)Br.O>C(Cl)Cl>[OH:4][C:5]1[CH:6]=[C:7]([C:15]2[C:16]([C:21]([NH:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:30]3[S:34][C:33]([CH2:35][C:36]([OH:38])=[O:37])=[CH:32][CH:31]=3)=[O:22])=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:8]=[C:9]([OH:13])[C:10]=1[OH:11]

Participants

6

Reactant 4

HCID 947NitrogenHCID 962WaterHCID 25134Boron tribromideHCID 59785707(5-{2-[(3',4',5'-Trimethoxy-biphenyl-2-carbonyl)-amino]-phenyl}-thiophen-2-yl)-acetic acid

Product 1

HCID 16116559(5-{2-[(3',4',5'-Trihydroxy-biphenyl-2-carbonyl)-amino]-phenyl}-thiophen-2-yl)-acetic acidYield 19.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

(The following reaction is done in an anhydrous N2 atmosphere.) Dissolve (5-{2-[(3′,4′,5′-Trimethoxy-biphenyl-2-carbonyl)-amino]-phenyl}-thiophen-2-yl)-acetic acid (86) (55 mg, 0.11 mmol) in anhydrous DCM (3.2 mL) at −78° C., add dropwise a 1M solution of BBr3 in DCM (730 μL, 0.73 mmol) and stir for additional 30 min at −78° C. After slowly warming up stir the reaction solution for additional 4 h at rt. Cool reaction mixture to 0° C., add dropwise water. Extract the mixture with EtOAc (3×), wash combined organic layer with brine and dry it with Na2SO4. Purify the crude product by preparative RP HPLC (gradient, water/CH3CN 95:5 to 5:95) to obtain (5-{2-[(3′,4′,5′-Trihydroxy-biphenyl-2-carbonyl)-amino]-phenyl}-thiophen-2-yl)-acetic acid (87) (10 mg, 18%) as a yellow solid. 1H NMR (400 MHz, CD3OD): 3.88 (s, 2H); 6.50 (s, 2H); 6.66 (d, 1H, J=3.5 Hz); 6.93 (d, 1H, J=3.5 Hz); 7.23 (t; 1H, J=7.3 Hz); 7.35 (t, 1H, J=7.6 Hz); 7.38-7.46 (m, 3H); 7.50 (t, 1H, J=7.3 Hz); 7.62 (d, 1H, J=8.0 Hz); 7.84 (d, 1H, J=8.0 Hz).

Workup

  1. custom(The following reaction
  2. temperatureAfter slowly warming up
  3. stirringstir the reaction solution for additional 4 h at rt
  4. temperatureCool
  5. customreaction mixture to 0° C.
  6. extractionExtract the mixture with EtOAc (3×)
  7. washwash
  8. dry with materialdry it with Na2SO4
  9. customPurify the crude product by preparative RP HPLC (gradient, water/CH3CN 95:5 to 5:95)

Sources & evidence

ORD record
ord-23b73798a9944136b7dc9d06cec6fca2
Source dataset
uspto-grants-2013_02
Patent number
US08367677B2

Reaction notes

Loading…