2-Chlorobenzoic Acid → HCID 19024441, compound

HRID 1033805Notes

Reaction equation

HRID 1033805 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH2:23]([N:28]([CH2:40][C:41]1[CH:46]=[CH:45][C:44]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][C:48]=2[S:53](=[O:56])(=[O:55])[NH2:54])=[CH:43][CH:42]=1)[C:29]([N:31]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH2:33][CH2:32]1)=[O:30])[CH2:24][CH2:25][CH2:26][CH3:27].N12CCCN=C1CCCCC2>C1COCC1>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH:54][S:53]([C:48]1[CH:49]=[CH:50][CH:51]=[CH:52][C:47]=1[C:44]1[CH:43]=[CH:42][C:41]([CH2:40][N:28]([CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[C:29]([N:31]2[C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[CH2:33][CH2:32]2)=[O:30])=[CH:46][CH:45]=1)(=[O:56])=[O:55])=[O:6]

Participants

6

Reactant 4

HCID 83742-Chlorobenzoic AcidHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 19024447HCID 19024447, compound

Product 1

HCID 19024441HCID 19024441, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
55 °C

Procedure

A solution of 21 mg (0.13 mmole) of 2-chlorobenzoic acid and 22 mg (0.13 mmole) of 1,1'-carbonyldiimidazole (CDI) in 0.8 mL of THF was stirred under N2 at 65° C. for 2.5 hours. Subsequently, a solution of 32 mg (0.067 mmole) of 1-[N-pentyl-N-[(2'-sulfamoylbiphenyl-4-yl)methyl]carbamoyl]indoline (from Step B) and 20 μL (0.13 mmole) of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in 0.8 mL of THF was added. After stirring for 29 hours at 55° C., the mixture was partitioned between EtOAc and 5% citric acid (aqueous). The organic layer was washed with water and brine, then dried over sodium sulfate. After filtration and removal of volatiles, the crude product was flash chromatographed over silica gel (gradient elution with 0.5-1.0% MeOH in CH2Cl2) to give 28 mg (68%) of the title compound as an off-white solid, mp 83°-85° C.; homogeneous by TLC (95:5 MeOH--CH2Cl2); FAB-MS m/e 616 (M+1)+.

Workup

  1. customthe mixture was partitioned between EtOAc and 5% citric acid (aqueous)
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationAfter filtration and removal of volatiles
  5. customchromatographed over silica gel (gradient elution with 0.5-1.0% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-2a641906d4de45a2bdbf6204a7317a11
Source dataset
uspto-grants-1994_05
Patent number
US05312820

Reaction notes

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