4-Methylmorpholine → HCID 10288850, compound

HRID 1244721Notes

Reaction equation

HRID 1244721 reaction equation
[NH2:1][C@@H:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][C@H:3]1[NH:11][C:12]([C:14]1[NH:18][C:17]2[C:19]([Cl:23])=[C:20](Cl)[S:21][C:16]=2[CH:15]=1)=[O:13].[OH2:24].[OH:25]N1C2C=CC=CC=2N=N1.[ClH:35].C(N=C=N[CH2:41][CH2:42][CH2:43][N:44](C)C)C.CN1C[CH2:52][O:51]CC1>CN(C)C=O.ClCCl.FC(F)(F)C(O)=O>[NH2:44][C@H:43]([C:52]([OH:51])=[O:25])[CH2:42][C:41]([NH:1][C@@H:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][C@H:3]1[NH:11][C:12]([C:14]1[NH:18][C:17]2[C:19]([Cl:23])=[C:20]([Cl:35])[S:21][C:16]=2[CH:15]=1)=[O:13])=[O:24]

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 11772963HCID 11772963, compound

Product 1

HCID 10288850HCID 10288850, compoundYield 59.8%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

N-[(1R,2R)-1-Amino-2,3-dihydro-1H-inden-2-yl]-2,3-dichloro-4H-thieno[3,2-b]pyrrole-5-carboxamide (Method 8, 350 mg, 0.73 mmol) was added to a solution of N-alpha-t-Boc-L-aspartic acid alpha-t-butyl ester (232 mg, 0.80 mmol), 1-hydroxybenzotriazole monohydrate (123 mg, 0.80 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (154 mg, 0.80 mmol), 4-methylmorpholine (0.18 mL, 1.6 mmol) in N,N-dimethylformamide (20 mL). The mixture was stirred at ambient temperature for 16 hours. The volatiles were removed by evaporation and the residue was dissolved in ethyl acetate (20 mL) and water (10 mL), the layers were separated before washing with 2M HCl then saturated NaHCO3. Evaporation afforded a white solid which was redissolved in dichloromethane (5 mL) and trifluoroacetic acid (5 mL), the solution was allowed to stir at ambient temperature for 2 hours. The volatiles were removed by evaporation and the residue triturated with ether, collected by filtration, washed with ether (2×10 ml) and dried to give the title compound (210 mg, 48%) as a white solid.

Workup

  1. customThe volatiles were removed by evaporation
  2. dissolutionthe residue was dissolved in ethyl acetate (20 mL)
  3. customwater (10 mL), the layers were separated
  4. washbefore washing with 2M HCl
  5. customEvaporation
  6. customafforded a white solid which
  7. stirringto stir at ambient temperature for 2 hours
  8. customThe volatiles were removed by evaporation
  9. customthe residue triturated with ether
  10. filtrationcollected by filtration
  11. washwashed with ether (2×10 ml)
  12. customdried

Sources & evidence

ORD record
ord-e18757eebcc94bacb8f9fa6c7e0b14d2
Source dataset
uspto-grants-2006_10
Patent number
US07122567B2

Reaction notes

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