1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-(2-Fluoro-4-iodophenylamino)-1H-indazole-5-carboxylic acid ((R)-2,2-dimethyl-[1,3]-dioxolan-4-ylmethoxy)amide

HRID 79058Notes

Reaction equation

HRID 79058 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](O)=[O:20])=[CH:17][CH:16]=[C:15]2[C:11]=1[CH:12]=[N:13][NH:14]2.[CH3:22][C:23]1([CH3:31])[O:27][C@@H:26]([CH2:28][O:29][NH2:30])[CH2:25][O:24]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:22][C:23]1([CH3:31])[O:27][C@@H:26]([CH2:28][O:29][NH:30][C:19]([C:18]2[C:10]([NH:9][C:3]3[CH:4]=[CH:5][C:6]([I:8])=[CH:7][C:2]=3[F:1])=[C:11]3[C:15](=[CH:16][CH:17]=2)[NH:14][N:13]=[CH:12]3)=[O:20])[CH2:25][O:24]1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 11298047(R)-O-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)hydroxylamineHCID 575215054-(2-Fluoro-4-iodophenylamino)-1H-indazole-5-carboxylic acid

Product 1

HCID 866562454-(2-Fluoro-4-iodophenylamino)-1H-indazole-5-carboxylic acid ((R)-2,2-dimethyl-[1,3]-dioxolan-4-ylmethoxy)amideYield 68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(2-fluoro-4-iodophenylamino)-1H-indazole-5-carboxylic acid (150 mg, 0.38 mmol) and O—((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-hydroxylamine (83 mg, 0.57 mmol) in DMF (4 mL) was added EDCI (80 mg, 0.42 mmol), HOBt (56 mg, 0.42 mmol) and DIPEA (70 μL, 0.42 mmol). The reaction mixture was stirred at room temperature for 3.5 hours before being concentrated in vacuo. The resultant residue was dissolved in ethyl acetate (10 mL), washed with aqueous saturated sodium bicarbonate solution (10 mL) and the aqueous fraction 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—SPE, gradient 0-10% methanol in DCM) to yield the title compound as a pale yellow solid (135 mg, 68%). LCMS (Method B): RT=3.45 min, [M+H]+=527.

Workup

  1. concentrationbefore being concentrated in vacuo
  2. dissolutionThe resultant residue was dissolved in ethyl acetate (10 mL)
  3. washwashed with aqueous saturated sodium bicarbonate solution (10 mL)
  4. extractionthe aqueous fraction extracted twice with ethyl acetate (2×10 mL)
  5. washThe combined organic extracts were washed with brine (20 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cc3d63debd96423f8d88316c94e8cc24
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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