Triethylamine → 3-Cyano-5-[(1H-indazol-4-ylmethyl)-carbamoyl]-thiophene-2-carboxylic acid methyl ester

HRID 1952654Notes

Reaction equation

HRID 1952654 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:12]([OH:14])=O)=[CH:8][C:9]=1[C:10]#[N:11])=[O:4].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.Cl.Cl.[NH:58]1[C:66]2[C:61](=[C:62]([CH2:67][NH2:68])[CH:63]=[CH:64][CH:65]=2)[CH:60]=[N:59]1>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:12](=[O:14])[NH:68][CH2:67][C:62]2[CH:63]=[CH:64][CH:65]=[C:66]3[C:61]=2[CH:60]=[N:59][NH:58]3)=[CH:8][C:9]=1[C:10]#[N:11])=[O:4]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68226735(1H-Indazol-4-yl)methanamine dihydrochlorideHCID 682271093-Cyano-thiophene-2,5-dicarboxylic acid 2-methyl ester

Product 1

HCID 682266533-Cyano-5-[(1H-indazol-4-ylmethyl)-carbamoyl]-thiophene-2-carboxylic acid methyl esterYield 67.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-Cyano-thiophene-2,5-dicarboxylic acid 2-methyl ester (240 mg, 1.14 mmol) in anhydrous DMF (6 mL) was added triethylamine (0.64 mL, 4.56 mmol), HBTU (0.52 g, 1.36 mmol), HOBT (0.180 mg, 1.36 mmol), and C-(1H-Indazol-4-yl)-methylamine dihydrochloride (300 mg, 1.36 mmol). The mixture was stirred at room temperature 15 h, then quenched by pouring into EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash chromatography with 30-100% EtOAc in hexane to afford the desired product (0.2627 g, 67% yield).

Workup

  1. customquenched
  2. additionby pouring into EtOAc
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography with 30-100% EtOAc in hexane

Sources & evidence

ORD record
ord-876fa8563bbe46869f3b8673efe3a0ef
Source dataset
uspto-grants-2013_03
Patent number
US08404859B2

Reaction notes

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