Benzaldehyde → 2-[(Aminocarbonyl)amino]-5-[4-((3-hydroxypyrrolidin-1-yl)methyl)phenyl]thiophene-3-carboxamide

HRID 2421367Notes

Reaction equation

HRID 2421367 reaction equation
[NH2:1][C:2]([NH:4][C:5]1[S:6][C:7]([C:13]2[CH:18]=[CH:17][C:16]([CH:19]=O)=[CH:15][CH:14]=2)=[CH:8][C:9]=1[C:10]([NH2:12])=[O:11])=[O:3].[NH:21]1[CH2:25][CH2:24][CH:23]([OH:26])[CH2:22]1.C(OC)(OC)OC.C([BH3-])#N.C(=O)C1C=CC=CC=1>COCCOC.CN(C)C(=O)C.C(O)(=O)C>[NH2:1][C:2]([NH:4][C:5]1[S:6][C:7]([C:13]2[CH:14]=[CH:15][C:16]([CH2:19][N:21]3[CH2:25][CH2:24][CH:23]([OH:26])[CH2:22]3)=[CH:17][CH:18]=2)=[CH:8][C:9]=1[C:10]([NH2:12])=[O:11])=[O:3]

Participants

9

Reactant 5

HCID 240BenzaldehydeHCID 9005Trimethyl orthoformateHCID 982104-HydroxypyrrolidineHCID 498716Cyano-borohydrideHCID 219143262-[(Aminocarbonyl)amino]-5-[4-formylphenyl]thiophene-3-carboxamide

Product 1

HCID 219143032-[(Aminocarbonyl)amino]-5-[4-((3-hydroxypyrrolidin-1-yl)methyl)phenyl]thiophene-3-carboxamideYield 24.1%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 80711,2-DimethoxyethaneSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
80 °C

Procedure

2-[(Aminocarbonyl)amino]-5-(4-formylphenyl)-3-thiophenecarboxamide (100 mg) was stirred in a mixture of 1,2-dimethoxyethane (10 ml) and N,N-dimethylacetamide (5 ml). 3-pyrrolidinol (0.15 g) was added, followed by trimethyl orthoformate (5 ml) and acetic acid (0.5 ml). The reaction was stirred at 80° C. for 20 minutes, and then polymer-supported cyanoborohydride (0.45 g) was added. The reaction was stirred at 80° C. for a further 2 h, and then polymer-supported benzaldehyde (0.5 g) was added. The resins were removed by filtration, and the filtrate was then passed through a 5 g SCX column, washing with methanol (25 ml). The product was eluted using 1M methanolic ammonia (45 ml), and this solution was then evaporated to dryness under reduced pressure. Purification by chromatography on silica, eluting with dichloromethane/methanol (9:1), gave the product as an off-white solid (30 mg).

Workup

  1. stirringThe reaction was stirred at 80° C. for a further 2 h
  2. customThe resins were removed by filtration
  3. washwashing with methanol (25 ml)
  4. washThe product was eluted
  5. customthis solution was then evaporated to dryness under reduced pressure
  6. customPurification by chromatography on silica
  7. washeluting with dichloromethane/methanol (9:1)

Sources & evidence

ORD record
ord-af4190e29b214438ba6623bc331d9b91
Source dataset
uspto-grants-2011_06
Patent number
US07956084B2

Reaction notes

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