1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 59596660, compound

HRID 2264966Notes

Reaction equation

HRID 2264966 reaction equation
[Na+].[F:2][C:3]1[CH:8]=[C:7]([I:9])[CH:6]=[CH:5][C:4]=1[NH:10][C:11]1[C:15]2[CH:16]=[N:17][CH:18]=[CH:19][C:14]=2[N:13]([CH3:20])[C:12]=1[C:21]([O-:23])=O.[Si:24]([O:31][C@@H:32]([CH3:36])[CH2:33][O:34][NH2:35])([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C>C1COCC1.CN(C=O)C>[Si:24]([O:31][C@@H:32]([CH3:36])[CH2:33][O:34][NH:35][C:21]([C:12]1[N:13]([CH3:20])[C:14]2[CH:19]=[CH:18][N:17]=[CH:16][C:15]=2[C:11]=1[NH:10][C:4]1[CH:5]=[CH:6][C:7]([I:9])=[CH:8][C:3]=1[F:2])=[O:23])([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 58374418(S)-O-(2-((tert-Butyldimethylsilyl)oxy)propyl)hydroxylamineHCID 67212115HCID 67212115, compound

Product 1

HCID 59596660HCID 59596660, compoundYield 62.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

3-(2-Fluoro-4-iodo-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid sodium salt (0.20 g, 0.46 mmol), O—[(S)-2-(tert-butyldimethylsilanyloxy)-propyl]-hydroxylamine (95 mg, 0.46 mmol), HOBT (69 mg, 0.51 mmol), EDCI (97 mg, 0.51 mmol) and DIPEA (0.08 ml, 0.46 mmol) were suspended in a mixture of THF (3 ml) and DMF (1 ml). The reaction was stirred at room temperature for 16 hours. The reaction mixture was concentrated in vacuo and the residue dissolved in ethyl acetate (20 ml) and washed with aqueous saturated sodium bicarbonate solution (20 ml). The aqueous layer was isolated and extracted with ethyl acetate (2×10 ml) and the combined organic layers dried, washed with brine and dried over magnesium sulfate before concentrating in vacuo. The crude residue was purified by flash chromatography (SiO2, gradient 1-3% methanol in dichloromethane) to yield the title compound as an off-white solid (171 mg, 62%). LCMS (method B): RT=3.00 min, M+H+=599.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionthe residue dissolved in ethyl acetate (20 ml)
  3. washwashed with aqueous saturated sodium bicarbonate solution (20 ml)
  4. customThe aqueous layer was isolated
  5. extractionextracted with ethyl acetate (2×10 ml)
  6. customthe combined organic layers dried
  7. washwashed with brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationbefore concentrating in vacuo
  10. customThe crude residue was purified by flash chromatography (SiO2, gradient 1-3% methanol in dichloromethane)

Sources & evidence

ORD record
ord-39e88634122a43d4807db7cb4a10b53a
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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