Hydrochloric Acid → 6-cyclohexyl-3-[(dimethylamino)methyl]-5-phenyl-4H-thieno[3,2-b]pyrrole-2-carboxylic acid

HRID 505791Notes

Reaction equation

HRID 505791 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([O-:5])=[O:4].[C:8]([C:11]1[S:18][C:17]2[C:16]([CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)=[C:15]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[N:14](COC)[C:13]=2[C:12]=1[CH2:34][NH2+:35][CH2:36]C1CCS(=O)(=O)C1)([OH:10])=[O:9].C1(C2C3SC(C(O)=O)=C(C=O)C=3N(COC)C=2C2C=CC=CC=2)CCCCC1.CNC.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>ClCCCl.C1COCC1>[CH:19]1([C:16]2[C:17]3[S:18][C:11]([C:8]([OH:10])=[O:9])=[C:12]([CH2:34][N:35]([CH3:2])[CH3:36])[C:13]=3[NH:14][C:15]=2[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]1.[C:3]([OH:5])([C:2]([F:7])([F:6])[F:1])=[O:4]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 674DimethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 866270596-cyclohexyl-3-formyl-4-(methoxymethyl)-5-phenyl-4H-thieno[3,2-b]pyrrole-2-carboxylic acidHCID 87462708[2-Carboxy-6-cyclohexyl-4-(methoxymethyl)-5-phenyl-4h-thieno[3,2-b]pyrrol-3-yl]-n-[(1,1-dioxidotetrahydro-3-thienyl)methyl]methanaminium trifluoroacetate

Product 2

HCID 6422Trifluoroacetic acidHCID 111999266-cyclohexyl-3-[(dimethylamino)methyl]-5-phenyl-4H-thieno[3,2-b]pyrrole-2-carboxylic acidYield 29%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

Following the procedure described above for [2-carboxy-6-cyclohexyl-4-(methoxymethyl)-5-phenyl-4H-thieno[3,2-b]pyrrol-3-yl]-N-[(1,1-dioxidotetrahydro-3-thienyl)methyl]methanaminium trifluoroacetate (step 4), treatment of a solution (0.03 M) of 6-cyclohexyl-3-formyl-4-(methoxymethyl)-5-phenyl-4H-thieno[3,2-b]pyrrole-2-carboxylic acid in 1,2-dichloroethane with dimethylamine (2 M solution in THF, 1.2 eq.) and sodium triacetoxyborohydride (1.5 eq.) gave a residue that was dissolved in THF. The resulting solution (0.1 M) was treated with aqueous of HCl (1 N, 8 eq.) and the mixture was heated to 60° C. for 26 h. After cooling down, the mixture was concentrated to give a residue that 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 (29%) as its TFA salt.

Workup

  1. customgave a residue that
  2. temperatureAfter cooling down
  3. concentrationthe mixture was concentrated
  4. customto give a residue that
  5. customwas purified by RP-HPLC (Conditions

Sources & evidence

ORD record
ord-0bca2b7f49a44add8f98855b8914cb4e
Source dataset
uspto-grants-2010_08
Patent number
US07781431B2

Reaction notes

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