Lithium Hydroxide → HCID 67224573, compound

HRID 1951648Notes

Reaction equation

HRID 1951648 reaction equation
C[C:2]1[S:9][C:8]2[CH:7]=[CH:6][N:5]([CH2:10][C:11]3[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=3)[C:4]=2[C:3]=1[C:21](O)=[O:22].C[O:25][C:26](=[O:36])[C:27]1[CH:32]=[CH:31][C:30]([C@@H:33]([NH2:35])[CH3:34])=[CH:29][CH:28]=1.Cl.C(N=C=NCCCN(C)C)C.CN1CCOCC1.[Li+].[OH-]>CN(C=O)C.C1COCC1.O.CO>[F:20][C:17]([F:18])([F:19])[C:14]1[CH:15]=[CH:16][C:11]([CH2:10][N:5]2[CH:6]=[CH:7][C:8]3[S:9][CH:2]=[C:3]([C:21]([NH:35][C@H:33]([C:30]4[CH:31]=[CH:32][C:27]([C:26]([OH:25])=[O:36])=[CH:28][CH:29]=4)[CH3:34])=[O:22])[C:4]2=3)=[CH:12][CH:13]=1

Participants

10

Reactant 5

HCID 3939Lithium HydroxideHCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 17751895Methyl 4-((1S)-1-aminoethyl)benzoateHCID 671826242-Methyl-4-(4-(trifluoromethyl)benzyl)-4H-thieno[3,2-b]pyrrole-3-carboxylic acid

Product 1

HCID 67224573HCID 67224573, compoundYield 73.8%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 0.107 g of 2-methyl-4-(4-trifluoromethyl-benzyl)-4H-thieno[3,2-b]pyrrole-3-carboxylic acid, 0.150 g of (S)-4-(1-amino-ethyl)-benzoic acid methyl ester, 0.100 g of HOBT-hydrate, 0.133 g of ethyl-dimethylaminopropyl-carbodiimide hydrochloride (EDCI) and 0.150 ml of N-methylmorpholine in 4 ml of DMF was stirred at room temperature for 18 h. The reaction was then quenched with 2 ml of water and 5 ml of sat. NaHCO3 solution. The resulting mixture extracted with 20 ml of EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated to give the crude methyl ester which was dissolved in 4 ml THF, 4 mL MeOH and 1 mL water and treated with 1 mL of 1N LiOH solution. After stirring for 24 h at room temperature, the reaction mixture was concentrated under reduced pressure to remove THF and MeOH. The residue was diluted with 4 mL of water and treated with 0.7 mL of AcOH with vigorous stirring. After stirring for 2 h, the solid was collected by filtration and air-dried to give 0.110 g of the title compound as a white powder.

Workup

  1. customThe reaction was then quenched with 2 ml of water and 5 ml of sat. NaHCO3 solution
  2. extractionThe resulting mixture extracted with 20 ml of EtOAc
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude methyl ester which
  7. stirringAfter stirring for 24 h at room temperature
  8. concentrationthe reaction mixture was concentrated under reduced pressure
  9. customto remove THF and MeOH
  10. additionThe residue was diluted with 4 mL of water
  11. additiontreated with 0.7 mL of AcOH with vigorous stirring
  12. stirringAfter stirring for 2 h
  13. filtrationthe solid was collected by filtration
  14. customair-dried

Sources & evidence

ORD record
ord-79e1f821b402465982714ad689290c2c
Source dataset
uspto-grants-2013_03
Patent number
US08404736B2

Reaction notes

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