3-Aminobenzamide → HCID 87091804, compound

HRID 1524299Notes

Reaction equation

HRID 1524299 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([NH2:7])=[O:6].C1N=CN([C:16](N2C=NC=C2)=[O:17])C=1.Cl.Cl.[CH3:25][N:26]1[CH2:31][CH2:30][C:29]2[N:32]=[C:33]([NH:35][C:36](=[O:48])[C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([CH:43]4[CH2:47][CH2:46][CH2:45][NH:44]4)[CH:38]=3)[S:34][C:28]=2[CH2:27]1.[C:49]([OH:55])([C:51]([F:54])([F:53])[F:52])=[O:50]>CN(C1C=CN=CC=1)C.CN(C=O)C.O>[F:52][C:51]([F:54])([F:53])[C:49]([OH:55])=[O:50].[C:5]([C:4]1[CH:3]=[C:2]([NH:1][C:16]([N:44]2[CH2:45][CH2:46][CH2:47][CH:43]2[C:39]2[CH:40]=[CH:41][CH:42]=[C:37]([C:36](=[O:48])[NH:35][C:33]3[S:34][C:28]4[CH2:27][N:26]([CH3:25])[CH2:31][CH2:30][C:29]=4[N:32]=3)[CH:38]=2)=[O:17])[CH:10]=[CH:9][CH:8]=1)(=[O:6])[NH2:7]

Participants

8

Reactant 4

HCID 16453-AminobenzamideHCID 6422Trifluoroacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 87091149HCID 87091149, compound

Product 1

HCID 87091804HCID 87091804, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
90 °C

Procedure

Stir a solution of 3-aminobenzamide (51 mg, 0.362 mmol), CDI (60 mg, 0.362 mmol), and DMAP (45 mg, 0.362 mmol) in DMF (1.5 mL) at 90° C. for 30 min. A precipitate forms from the initial homogenous solution. Add N-(5-methyl-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-yl)-3-pyrrolidin-2-yl-benzamide di-HCl (100 mg, 0.241 mmol) to the hot reaction followed by more DMF (1 mL) and continue heating at 90° C. for 20 min. Cool the reaction to room temperature, dilute with water (1 mL), acidify with TFA (0.2 mL), and purify directly by reverse phase prep HPLC. Concentrate the fractions containing product to a solid which contains symmetric benzamide urea (30%). Suspend the solid in MeOH (4 mL) and sonicate—filter off the solid side product washing with MeOH (1 mL). Concentrate the filtrate, dry the residue in vacuo and triturate in EtOAc and hexane to give the title compound as a solid (97 mg). MS, electrospray 505.4 (M+H), rt 1.05 min.

Workup

  1. temperatureCool
  2. customthe reaction to room temperature
  3. custompurify directly by reverse phase prep HPLC
  4. concentrationConcentrate the fractions
  5. additioncontaining product to a solid which
  6. filtrationsonicate—filter off the solid side product
  7. washwashing with MeOH (1 mL)
  8. concentrationConcentrate the filtrate
  9. customdry the residue in vacuo
  10. customtriturate in EtOAc

Sources & evidence

ORD record
ord-ca68d3650b6448d6a3e9721c2b9a8825
Source dataset
uspto-grants-2015_07
Patent number
US09079880B2

Reaction notes

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