Water → HCID 66870734, compound

HRID 407559Notes

Reaction equation

HRID 407559 reaction equation
C(O)(C(F)(F)F)=O.[CH:8]([C:11]1[N:12]=[C:13]([C:16]2[CH:25]=[C:24]([O:26][CH:27]3[CH2:45][CH:44]4[N:29]([C:30](=[O:65])[N:31](CC5C=CC(OC)=CC=5)[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH:37]=[CH:38][CH:39]5[C:41]([C:47]([NH:49][S:50]([CH:53]6[CH2:55][CH2:54]6)(=[O:52])=[O:51])=[O:48])([NH:42][C:43]4=[O:46])[CH2:40]5)[CH2:28]3)[C:23]3[C:18](=[C:19]([CH3:68])[C:20]([O:66][CH3:67])=[CH:21][CH:22]=3)[N:17]=2)[S:14][CH:15]=1)([CH3:10])[CH3:9].O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH:8]([C:11]1[N:12]=[C:13]([C:16]2[CH:25]=[C:24]([O:26][CH:27]3[CH2:45][CH:44]4[N:29]([C:30](=[O:65])[NH:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH:37]=[CH:38][CH:39]5[C:41]([C:47]([NH:49][S:50]([CH:53]6[CH2:55][CH2:54]6)(=[O:52])=[O:51])=[O:48])([NH:42][C:43]4=[O:46])[CH2:40]5)[CH2:28]3)[C:23]3[C:18](=[C:19]([CH3:68])[C:20]([O:66][CH3:67])=[CH:21][CH:22]=3)[N:17]=2)[S:14][CH:15]=1)([CH3:10])[CH3:9]

Participants

6

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 66870829HCID 66870829, compound

Product 1

HCID 66870734HCID 66870734, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (10 mL) was added to a solution of N-[[18-[2-[4-(isopropyl)thiazol-2-yl]-7-methoxy-8-methylquinolin-4-yloxy]-2,15-dioxo-14-(4-methoxybenzyl)-3,14,16-triazatricyclo[14.3.0.04,6]nonadec-7-en-4-yl]carbonyl](cyclopropyl)sulfonamide (90) in DCM (20 mL). After 30 min at room temperature, water (20 mL) was added to the reaction mixture and the pH was adjusted to 3-4 with NaHCO3. The organic layer was washed with brine, dried (Na2SO4), filtered and evaporated. The residue was purified by column chromatography (gradient MeOH/CH2Cl2, 0:1 to 1:99, then AcOEt/CH2Cl2 1:1) to afford 313 mg (73%) of the desired title product 91 as a yellowish solid: m/z=751 (M+H)+. 1H-NMR (CDCl3): 0.88-1.64 (m, 16H), 1.96 (m, 2H), 2.52 (m, 1H), 2.68 (m s, 5H), 2.79-2.92 (m, 3H), 3.18 (m, 1H), 3.63-3.69 (m, 2H), 3.86 (m, 1H), 3.97 (s, 3H), 4.34 (m, 1H), 4.59 (m, 1H), 5.08 (m, 1H), 5.40 (m, 1H), 5.80 (m, 1H), 6.73 (s, 1H), 7.03 (s, 1H), 7.21 (d, J=8.9 Hz, 1H), 7.26 (br s, 1H), 7.47 (s, 1H), 7.92 (d, J=8.9 Hz, 1H), 10.20 (br s, 1H).

Workup

  1. washThe organic layer was washed with brine
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was purified by column chromatography (gradient MeOH/CH2Cl2, 0:1 to 1:99

Sources & evidence

ORD record
ord-f81e724cbf4e4e8ebb802df04ebe6331
Source dataset
uspto-grants-2014_06
Patent number
US08754106B2

Reaction notes

Loading…