1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 86656241, compound

HRID 79048Notes

Reaction equation

HRID 79048 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[C:18]([C:19]([OH:21])=O)=[CH:17][CH:16]=[C:15]2[C:11]=1[CH:12]=[N:13][N:14]2[S:22]([C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=1)(=[O:24])=[O:23].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[CH:53]([O:55][CH2:56][CH2:57][O:58][NH2:59])=[CH2:54].CCN(C(C)C)C(C)C>CN(C=O)C>[CH:53]([O:55][CH2:56][CH2:57][O:58][NH:59][C:19]([C:18]1[C:10]([NH:9][C:3]2[CH:4]=[CH:5][C:6]([I:8])=[CH:7][C:2]=2[F:1])=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([S:22]([C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=1)(=[O:23])=[O:24])[N:13]=[CH:12]2)=[O:21])=[CH2:54]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 670840434-(2-Fluoro-4-iodo-phenylamino)-1-(toluene-4-sulfonyl)-1H-indazole-5-carboxylic acid

Product 1

HCID 86656241HCID 86656241, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(2-fluoro-4-iodo-phenylamino)-1-(toluene-4-sulfonyl)-1H-indazole-5-carboxylic acid (0.58 g, 1.05 mmol) in DMF (10 mL) was added EDCI (0.22 g, 1.1 mmol) followed by HOBt (0.16 g, 1.1 mmol) and the reaction mixture stirred at room temperature for 10 minutes. O-(2-vinyloxy-ethyl)-hydroxylamine (0.12 g, 1.1 mmol) and DIPEA (0.2 mL, 1.1 mmol) were added and the reaction stirred for 16 hours before being concentrated in vacuo. The resultant residue was dissolved in ethyl acetate (10 mL), washed with an aqueous saturated sodium bicarbonate solution (10 mL) before the aqueous fraction was extracted twice with ethyl acetate (2×10 mL). The combined organic extracts were washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—PPC, gradient 0-100% ethyl acetate in cyclohexane) to yield the title compound as a pale brown solid (439 mg, 66%). LCMS (Method B): RT=4.40 min, [M+H]+=637.

Workup

  1. stirringthe reaction stirred for 16 hours
  2. concentrationbefore being concentrated in vacuo
  3. dissolutionThe resultant residue was dissolved in ethyl acetate (10 mL)
  4. washwashed with an aqueous saturated sodium bicarbonate solution (10 mL) before the aqueous fraction
  5. extractionwas extracted twice with ethyl acetate (2×10 mL)
  6. washThe combined organic extracts were washed with brine (20 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4bab65d3e5eb4a26ab6cd9f33c425431
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

Loading…