Morpholine → methyl 5-(4-chlorophenyl)-6-cyclohexyl-4-(2-morpholin-4-yl-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate

HRID 505813Notes

Reaction equation

HRID 505813 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH2:13][C:14](O)=[O:15])[C:11]3[CH:17]=[C:18]([C:20]([O:22][CH3:23])=[O:21])[S:19][C:10]=3[C:9]=2[CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)=[CH:4][CH:3]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:12]([CH2:13][C:14]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)=[O:15])[C:11]3[CH:17]=[C:18]([C:20]([O:22][CH3:23])=[O:21])[S:19][C:10]=3[C:9]=2[CH:24]2[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68472059[5-(4-chlorophenyl)-6-cyclohexyl-2-(methoxycarbonyl)-4H-thieno[3,2-b]pyrrol-4-yl]acetic acid

Product 1

HCID 11432036methyl 5-(4-chlorophenyl)-6-cyclohexyl-4-(2-morpholin-4-yl-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylateYield 51%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution (0.05 M) of [5-(4-chlorophenyl)-6-cyclohexyl-2-(methoxycarbonyl)-4H-thieno[3,2-b]pyrrol-4-yl]acetic acid in DMF at RT was treated with morpholine (2 eq.), DIEA (1.5 eq.) and HATU (2.5 eq.). The mixture was stirred at RT for 8 h, then it was diluted with DCM and washed sequentially with aqueous HCl (1 N), aqueous NaHCO3 (saturated solution) and dried. Evaporation of the solvent under reduced pressure gave a residue which was purified by RP-HPLC (Conditions: Waters X-TERRA MS C18, 10 micron, 19×150 mm; flow: 20 mL/min; Gradient: A: H2O+0.05% TFA; B: MeCN+0.05% TFA; 90% A isocratic for 2 min then linear to 10% A in 9 min) to afford the title compound (51%) as a solid.

Workup

  1. washwashed sequentially with aqueous HCl (1 N), aqueous NaHCO3 (saturated solution)
  2. customdried
  3. customEvaporation of the solvent under reduced pressure
  4. customgave a residue which
  5. customwas purified by RP-HPLC (Conditions
  6. wait90% A isocratic for 2 min then linear to 10% A in 9 min

Sources & evidence

ORD record
ord-6d800910a5ce4f75b60b7a531d0f7008
Source dataset
uspto-grants-2010_08
Patent number
US07781431B2

Reaction notes

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