Benzaldehyde → 1-(3-Carbamoyl-5-(4-(((2-hydroxyethyl)(methyl)amino)methyl)phenyl)thiophen-2-yl)urea

HRID 2101212Notes

Reaction equation

HRID 2101212 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].[CH3:21][NH:22][CH2:23][CH2:24][OH:25].C(OC)(OC)OC.C([BH3-])#N.C(=O)C1C=CC=CC=1>COCCOC.CC(N(C)C)=O.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:22]([CH2:23][CH2:24][OH:25])[CH3:21])=[CH:17][CH:18]=2)=[CH:8][C:9]=1[C:10]([NH2:12])=[O:11])=[O:3]

Participants

9

Reactant 5

HCID 240BenzaldehydeHCID 80162-(Methylamino)ethanolHCID 9005Trimethyl orthoformateHCID 498716Cyano-borohydrideHCID 219143262-[(Aminocarbonyl)amino]-5-[4-formylphenyl]thiophene-3-carboxamide

Product 1

HCID 445608061-(3-Carbamoyl-5-(4-(((2-hydroxyethyl)(methyl)amino)methyl)phenyl)thiophen-2-yl)ureaYield 59.8%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 80711,2-DimethoxyethaneSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
80 °C

Procedure

2-[(Aminocarbonyl)amino]-5-[4-formylphenyl]thiophene-3-carboxamide (0.1 g) was stirred in a mixture of DME (10 ml) and DMA(5 ml). 2-(Methylamino)ethanol (0.13 g) was added, followed by trimethyl orthoformate (5 ml) and acetic acid (0.5 ml). The reaction was stirred at 80° C. for 20 min, 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 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 evaporated to dryness under reduced pressure. Purification by chromatography on silica, eluting with DCM/methanol (9:1), gave the product as an off-white solid (0.072 g). MS (ES) 349 (M+H)+. 1H NMR (DMSO-D6) 2.15 (s, 3H), 2.45 (m, 2H), 3.50 (m, 4H), 4.35 (t, 1H), 6.90 (s, 2H), 7.25-7.40 (m, 3H), 7.50 (d, 2H), 7.70 (s, 1H), 7.75 (s, 1H), 11.00 (s, 11).

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 evaporated to dryness under reduced pressure
  6. customPurification by chromatography on silica
  7. washeluting with DCM/methanol (9:1)

Sources & evidence

ORD record
ord-05093b3d1ce94808aa5b83b59db24089
Source dataset
uspto-grants-2009_08
Patent number
US07572826B2

Reaction notes

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