Trifluoroacetic acid → HCID 86631967, compound

HRID 1162496Notes

Reaction equation

[C:1]([NH:4][C:5]1[N:6]=[C:7]2[CH:12]=[CH:11][C:10]([C:13]3[CH:14]=[N:15][C:16]([Cl:33])=[C:17]([NH:19][S:20]([C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH:30]([F:32])[F:31])[CH:24]=4)(=[O:22])=[O:21])[CH:18]=3)=[N:9][N:8]2[C:34]=1[C:35]1[CH2:40][CH2:39][N:38](C(OC(C)(C)C)=O)[CH2:37][CH:36]=1)(=[O:3])[CH3:2].FC(F)(F)C(O)=O>>[Cl:33][C:16]1[N:15]=[CH:14][C:13]([C:10]2[CH:11]=[CH:12][C:7]3[N:8]([C:34]([C:35]4[CH2:40][CH2:39][NH:38][CH2:37][CH:36]=4)=[C:5]([NH:4][C:1](=[O:3])[CH3:2])[N:6]=3)[N:9]=2)=[CH:18][C:17]=1[NH:19][S:20]([C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH:30]([F:31])[F:32])[CH:24]=1)(=[O:21])=[O:22]

Participants

Reactant 2

HCID 6422Trifluoroacetic acid

HCID 57749439tert-butyl 4-(2-acetamido-6-(6-chloro-5-(3-(difluoromethoxy)phenylsulfonamido)pyridin-3-yl)imidazo[1,2-b]pyridazin-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 86631967HCID 86631967, compound

Procedure

A sealable vial was charged with tert-butyl 4-(2-acetamido-6-(6-chloro-5-(3-(difluoromethoxy)phenylsulfonamido)pyridin-3-yl)imidazo[1,2-b]pyridazin-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate (104.0 mg, 151 μmol) and neat trifluoroacetic acid (1.16 mL, 15.1 mmol). The solution was stirred at rt for 1 h. The solution was then concentrated to give N-(6-(6-chloro-5-(3-(difluoromethoxy)phenylsulfonamido)pyridin-3-yl)-3-(1,2,3,6-tetrahydropyridin-4-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide, which was of sufficient purity for further use. Methanol (2.0 mL) was added to the crude residue followed by an aqueous solution of sodium hydroxide (6 N, 502 μl, 3014 μmol). The solution was heated at 50° for 18 h. The solution was concentrated, then taken up in minimal MeOH/DMSO and purified by preparative HPLC (Gilson GX-218, Middletown, Wis.: 5-90% (0.1% TFA in CH3CN) in H2O over 15 min, Phenomenex, Zorbax 00F-4435-UO 150×30 mm, 5 micron) to afford the title compound, N-(5-(2-amino-3-(1,2,3,6-tetrahydropyridin-4-yl)imidazo[1,2-b]pyridazin-6-yl)-2-chloropyridin-3-yl)-3-(difluoromethoxy)benzenesulfonamide (8.6 mg, 8.6% yield) as a yellow solid. LCMS (ESI positive ionization) m/z: 548.1 (M+1); 1H NMR (400 MHz, MeOH) δ ppm 3.12-3.23 (m, 2H); 3.59 (t, J=5.97 Hz, 2H); 3.97-4.08 (m, 2H); 6.35-6.48 (m, 1H); 6.84 (t, J=73.02 Hz, 1H); 7.40-7.46 (m, 1H); 7.49-7.66 (m, 3H); 7.87-7.94 (m, 1H); 7.97-8.04 (m, 1H); 8.79 (dd, J=15.55, 2.25 Hz, 2H).

Workup

concentrationThe solution was then concentrated

Sources & evidence

ORD record: ord-3fbbe7b7439146f3ac90bed63304d97b
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07820665B2

Reaction notes

Loading…