Succinic Acid → Batefenterol Succinate

HRID 2423017Notes

Reaction equation

HRID 2423017 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][NH:9][CH2:10][C@H:11]([OH:24])[C:12]2[CH:21]=[CH:20][C:19]([OH:22])=[C:18]3[C:13]=2[CH:14]=[CH:15][C:16](=[O:23])[NH:17]3)[C:5]([O:25][CH3:26])=[CH:4][C:3]=1[NH:27][C:28]([CH2:30][CH2:31][N:32]1[CH2:37][CH2:36][CH:35]([O:38][C:39](=[O:53])[NH:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=2[C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[CH2:34][CH2:33]1)=[O:29].[C:54]([OH:61])(=[O:60])[CH2:55][CH2:56][C:57]([OH:59])=[O:58]>O1CCCC1.CO>[C:54]([OH:61])(=[O:60])[CH2:55][CH2:56][C:57]([OH:59])=[O:58].[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][NH:9][CH2:10][C@H:11]([OH:24])[C:12]2[CH:21]=[CH:20][C:19]([OH:22])=[C:18]3[C:13]=2[CH:14]=[CH:15][C:16](=[O:23])[NH:17]3)[C:5]([O:25][CH3:26])=[CH:4][C:3]=1[NH:27][C:28]([CH2:30][CH2:31][N:32]1[CH2:37][CH2:36][CH:35]([O:38][C:39](=[O:53])[NH:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=2[C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH2:34][CH2:33]1)=[O:29]

Participants

5

Reactant 2

HCID 1110Succinic Acid3×HCID 10372836Batefenterol

Product 1

HCID 16718568Batefenterol Succinate

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent3×

Procedure

Biphenyl-2-ylcarbamic acid 1-[2-(2-chloro-4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-5-methoxyphenylcarbamoyl)-ethyl]piperidin-4-yl ester (200 mg) was suspended in tetrahydrofuran (1.5 ml) at ˜70° C. A first portion (100 μl) of succinic acid in methanol was added, from a total of succinic acid (33.5 mg, 1.05 equiv) in THF (0.5 ml) and the temperature reduced to 50° C. The remaining succinic acid in methanol was added in four further portions over approximately 5 hours, with further THF (1 ml) added after 1 h, to replace lost solvent. After a further 30 min, the resulting slurry was temperature cycled between 0° C. and 40° C. over 5 days. The resulting solid was isolated by filtration, washed with methanol, dried on filter paper overnight and then in a vacuum oven, to provide the title compound as a crystalline solid (140 mg).

Workup

  1. customreduced to 50° C
  2. additionadded after 1 h
  3. customtemperature cycled between 0° C. and 40° C.
  4. customover 5 days
  5. customThe resulting solid was isolated by filtration
  6. washwashed with methanol
  7. customdried
  8. filtrationon filter paper overnight

Sources & evidence

ORD record
ord-41d74a27651f474998739b514be6eecd
Source dataset
uspto-grants-2011_06
Patent number
US07960551B2

Reaction notes

Loading…