Triethylamine → 1-[3-[(N-Benzyl pyrrolidin-3-yl)carbamoyl]phenylcarbamoyl]-5-methylthio-6-trifluoromethyl indoline

HRID 1740811Notes

Reaction equation

HRID 1740811 reaction equation
[CH3:1][S:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[C:12]([F:15])([F:14])[F:13])[N:8]([C:16](=[O:27])[NH:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([C:24](O)=[O:25])[CH:19]=1)[CH2:7][CH2:6]2.C(Cl)(=O)C(Cl)=O.C(N(CC)CC)C.[NH2:41][CH:42]1[CH2:46][CH2:45][N:44]([CH2:47][C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[CH2:43]1>ClCCl.C1COCC1.CN(C=O)C>[CH2:47]([N:44]1[CH2:45][CH2:46][CH:42]([NH:41][C:24]([C:20]2[CH:19]=[C:18]([NH:17][C:16]([N:8]3[C:9]4[C:5](=[CH:4][C:3]([S:2][CH3:1])=[C:11]([C:12]([F:15])([F:14])[F:13])[CH:10]=4)[CH2:6][CH2:7]3)=[O:27])[CH:23]=[CH:22][CH:21]=2)=[O:25])[CH2:43]1)[C:48]1[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 27566131-Benzyl-3-aminopyrrolidineHCID 180051075-Methylthio-6-trifluoromethyl-1-(3-carboxy Phenyl Carbamoyl)indoline

Product 1

HCID 218330711-[3-[(N-Benzyl pyrrolidin-3-yl)carbamoyl]phenylcarbamoyl]-5-methylthio-6-trifluoromethyl indolineYield 89.4%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

The carboxylic acid from Example 12 (0.5 g, 1.25 mmol) in dichloromethane (10 ml) was treated with oxalyl chloride (0.3 ml, 3.4 mmol) and DMF (catalytic). The solution was stirred for 1 hour and evaporated to dryness. The residue in dry THF (3 ml) was added to a stirred solution of triethylamine (0.3ml, 4 mmol) and 3-amino-N-benzyl pyrrolidine (0.79 g, 4.5 mmol) in dry THF (10 ml). Following 3 hours at room temperature the solution was partitioned (H2O/EtOAc). Drying and removal of solvent followed by rexst (EtOAc/60°-80° C. petrol) afforded the title compound (0.62 g, 89%) as a white powder. M.pt. 174°-175° C.

Workup

  1. customevaporated to dryness
  2. waitFollowing 3 hours at room temperature
  3. customthe solution was partitioned (H2O/EtOAc)
  4. customDrying
  5. customremoval of solvent
  6. customfollowed by rexst (EtOAc/60°-80° C. petrol)

Sources & evidence

ORD record
ord-4446ed561dc24c1f8e7af2e8d3fe5339
Source dataset
uspto-grants-1999_10
Patent number
US05972937

Reaction notes

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