1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 59140134, compound

HRID 1500723Notes

Reaction equation

HRID 1500723 reaction equation
[F:1][C:2]1[C:3]2[N:4]([CH:20]=[N:21][CH:22]=2)[C:5]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=2[F:19])=[C:6]([C:8]([OH:10])=O)[CH:7]=1.[CH3:23][C:24]1([CH3:32])[O:28][C@H:27]([CH2:29]NO)[CH2:26][O:25]1.CCN=C=NCCCN(C)C.C1C=CC2[N:52]([OH:53])N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:32][C:24]1([CH3:23])[O:28][C@@H:27]([CH2:29][O:53][NH:52][C:8]([C:6]2[CH:7]=[C:2]([F:1])[C:3]3[N:4]([CH:20]=[N:21][CH:22]=3)[C:5]=2[NH:11][C:12]2[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=2[F:19])=[O:10])[CH2:26][O:25]1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 23541087(S)-(+)-2,2-Dimethyl-4-hydroxyaminomethyl-1,3-dioxolaneHCID 59140183HCID 59140183, compound

Product 1

HCID 59140134HCID 59140134, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

8-Fluoro-5-(2-fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (235 mg, 0.57 mmol), O—(((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-hydroxylamine (92 mg, 0.62 mmol), EDCI (120 mg, 0.62 mmol), HOBt (84 mg, 0.62 mmol) and DIPEA (0.1 mL, 0.62 mmol) were dissolved in DMF (10 mL) and the reaction mixture stirred at room temperature for 72 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 fractions were washed with brine (20 mL), dried with MgSO4 and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0-10% methanol in DCM) to yield the title compound as a pale yellow solid (298 mg, 97%). LCMS (Method B): RT=3.34 min, [M+H]+=545.

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 fractions were washed with brine (20 mL)
  6. dry with materialdried with MgSO4
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f81c2616f9f04a3380166e62bfda4cf7
Source dataset
uspto-grants-2015_12
Patent number
US09206174B2

Reaction notes

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