Nitrogen → HCID 59819846, compound

HRID 383604

Reaction equation

N#N.[CH3:3][O:4][C:5](=[O:36])[CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[NH:19][C:20](=[O:35])[CH2:21][CH2:22][C:23]2[CH:28]=[C:27]([O:29]C)[C:26]([O:31]C)=[C:25]([O:33]C)[CH:24]=2)[CH:10]=[CH:11][CH:12]=1.B(Br)(Br)Br>C(Cl)Cl>[CH3:3][O:4][C:5](=[O:36])[CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[NH:19][C:20](=[O:35])[CH2:21][CH2:22][C:23]2[CH:24]=[C:25]([OH:33])[C:26]([OH:31])=[C:27]([OH:29])[CH:28]=2)[CH:10]=[CH:11][CH:12]=1

Participants

Conditions

Temperature: -78 °C

Procedure

(The following reaction is done in an anhydrous N2 atmosphere.) Dissolve {2′-[3-(3,4,5-Trimethoxy-phenyl)-propionylamino]-biphenyl-3-yl}-acetic acid methyl ester (72) (46 mg, 0.10 mmol) in anhydrous DCM (1.0 mL), cool the solution to −78° C. and add dropwise BBr3 (85 μL, 0.90 mmol). Stir the reaction mixture for 30 min at −78° C. and after slowly warming up for additional 2 h at rt. Add dropwise ice water, separate layers and extract aqu. layer with DCM (3 times). Wash combined organic layer with brine and dry with Na2SO4. Purify the crude product by preparative RP HPLC (gradient, water/CH3CN 95:5 to 5:95) to obtain {2′-[3-(3,4,5-Trihydroxy-phenyl)-propionylamino]-biphenyl-3-yl}-acetic acid methyl ester (73) (2 mg, 5%). 1H NMR (400 MHz, CD3CN): 2.43 (t, 2H, J=7.6 Hz); 2.69 (t, 2H, J=7.6 Hz); 3.66 (s, 3H); 3.70 (s, 2H); 6.25 (s, 2H); 7.18-7.34 (m, 5 H); 7.35-7.44 (m, 2H); 7.65 (br.s, 1H); 7.89 (br.d, 1H, J=8.3 Hz).

Workup

custom(The following reaction
temperatureafter slowly warming up for additional 2 h at rt
customseparate layers
extractionextract aqu
washWash
dry with materialdry with Na2SO4
customPurify the crude product by preparative RP HPLC (gradient, water/CH3CN 95:5 to 5:95)

Sources & evidence

ORD record: ord-a9dcd5bfeff7454cb3cd57ea2b25269b
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08367677B2

Linked notes

Loading…