2-Mercaptobenzoic Acid → N-(2-{2-Methyl-4-[((S)-phenyl-(S)-piperidin-2-yl-methyl)-amino]-quinolin-8-yloxy}-ethyl)methanesulfonamide dihydrochloride

HRID 1966526Notes

Reaction equation

HRID 1966526 reaction equation
C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([N:34]1[CH2:39][CH2:38][CH2:37][CH2:36][C@H:35]1[C@@H:40]([NH:47][C:48]1[C:57]2[C:52](=[C:53]([O:58][CH2:59][CH2:60][NH:61][S:62]([CH3:65])(=[O:64])=[O:63])[CH:54]=[CH:55][CH:56]=2)[N:51]=[C:50]([CH3:66])[CH:49]=1)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)C=C.SC1C=CC=CC=1C(O)=O.[OH-].[Na+].C(O)(C)C.O.[ClH:84]>C1COCC1>[ClH:84].[ClH:84].[CH3:66][C:50]1[CH:49]=[C:48]([NH:47][C@@H:40]([C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)[C@@H:35]2[CH2:36][CH2:37][CH2:38][CH2:39][NH:34]2)[C:57]2[C:52](=[C:53]([O:58][CH2:59][CH2:60][NH:61][S:62]([CH3:65])(=[O:63])=[O:64])[CH:54]=[CH:55][CH:56]=2)[N:51]=1

Participants

7

Reactant 5

HCID 54432-Mercaptobenzoic AcidHCID 14798Sodium HydroxideHCID 821241,4-Bis(diphenylphosphino)butaneHCID 21409480Isopropanol-hcl-waterHCID 59474734N-[2-(4-{[(S)-((S)-1-Allylpiperidin-2-yl)-phenylmethyl]-amino}-2-methylquinolin-8-yloxy)ethyl]methanesulfonamide

Product 1

HCID 68498582N-(2-{2-Methyl-4-[((S)-phenyl-(S)-piperidin-2-yl-methyl)-amino]-quinolin-8-yloxy}-ethyl)methanesulfonamide dihydrochlorideYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Tris-(dibenzylidenaceton)-dipalladium(0) (19.0 mg, 0.021 mmole) and 1,4-bis(diphenylphosphino)butane (9 mg, 0.021 mmole) were mixed with THF (10 mL). N-[2-(4-{[(S)—((S)-1-Allylpiperidin-2-yl)-phenylmethyl]-amino}-2-methylquinolin-8-yloxy)-ethyl]-methanesulfonamide (example 35, 130 mg, 0.256 mmole) in THF (5 mL) and 2-mercaptobenzoic acid (86.7 mg, 0.562 mmole) in THF (5 mL) were added and the mixture was stirred at RT for 2 hrs. The content of the flask was mixed with 1N NaOH and extracted with dichloromethane. The organic layer was washed with water and saturated NaCl solution and concentrated. The residue thus obtained was cystallized from isopropanol/water/HCl to obtain a white solid (42 mg, 30%).

Workup

  1. extractionextracted with dichloromethane
  2. washThe organic layer was washed with water and saturated NaCl solution
  3. concentrationconcentrated
  4. customThe residue thus obtained

Sources & evidence

ORD record
ord-69cc82f3695b4a3b8d63c256525f999d
Source dataset
uspto-grants-2013_04
Patent number
US08420670B2

Reaction notes

Loading…