1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 5-(2-Fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid ((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amide

HRID 1500714Notes

Reaction equation

HRID 1500714 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[N:15]2[CH:16]=[N:17][CH:18]=[C:14]2[CH:13]=[CH:12][C:11]=1[C:19]([OH:21])=O.[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(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>C1COCC1.C(OCC)(=O)C>[CH3:22][C:23]1([CH3:31])[O:27][C@H:26]([CH2:28][O:29][NH:30][C:19]([C:11]2[CH:12]=[CH:13][C:14]3[N:15]([CH:16]=[N:17][CH:18]=3)[C:10]=2[NH:9][C:3]2[CH:4]=[CH:5][C:6]([I:8])=[CH:7][C:2]=2[F:1])=[O:21])[CH2:25][O:24]1

Participants

8

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 591401865-(2-Fluoro-4-iodophenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid

Product 1

HCID 866377245-(2-Fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid ((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-amideYield 84.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-(2-fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (326 mg, 0.82 mmol) in THF (4.1 ml) was added O—((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-hydroxylamine (362 mg, 2.46 mmol), DIPEA (1.26 ml, 7.4 mmol), HOBt (327 mg, 2.46 mmol) and EDCI (471 mg, 2.46 mmol), the mixture stirred for 18 hours at ambient temperature. The reaction mixture was diluted with ethyl acetate and washed with a saturated aqueous solution of sodium bicarbonate followed by water and then brine. The organic phase was isolated, dried (Na2SO4), filtered and concentrated in vacuo. Purification of the resultant residue by flash chromatography (Si-PPC, gradient 0% to 10%, methanol in dichloromethane) afforded the title compound as a pale yellow solid (364 mg, 84%). LCMS (method B): RT=2.58 min, [M+H]+=527.

Workup

  1. washwashed with a saturated aqueous solution of sodium bicarbonate
  2. customThe organic phase was isolated
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification of the resultant residue by flash chromatography (Si-PPC, gradient 0% to 10%, methanol in dichloromethane)

Sources & evidence

ORD record
ord-162468eb547a4500adf9d9000dd1cf75
Source dataset
uspto-grants-2015_12
Patent number
US09206174B2

Reaction notes

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