1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 8-(4-Cyclobutyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (2-vinyloxy-ethoxy)-amide

HRID 2067033Notes

Reaction equation

HRID 2067033 reaction equation
[CH:1]1([C:5]2[CH:10]=[CH:9][C:8]([NH:11][C:12]3[C:13]4[N:14]([CH:21]=[N:22][CH:23]=4)[CH:15]=[CH:16][C:17]=3[C:18]([OH:20])=O)=[C:7]([F:24])[CH:6]=2)[CH2:4][CH2:3][CH2:2]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[CH:55]([O:57][CH2:58][CH2:59][O:60][NH2:61])=[CH2:56]>C1COCC1>[CH:55]([O:57][CH2:58][CH2:59][O:60][NH:61][C:18]([C:17]1[CH:16]=[CH:15][N:14]2[CH:21]=[N:22][CH:23]=[C:13]2[C:12]=1[NH:11][C:8]1[CH:9]=[CH:10][C:5]([CH:1]2[CH2:4][CH2:3][CH2:2]2)=[CH:6][C:7]=1[F:24])=[O:20])=[CH2:56]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 595652038-(4-Cyclobutyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid

Product 1

HCID 595651898-(4-Cyclobutyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (2-vinyloxy-ethoxy)-amideYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 8-(4-cyclobutyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (154 mg, 0.46 mmol), EDCI (105 mg, 0.55 mmol), HOBt (74 mg, 0.55 mmol), DIPEA (0.19 mL, 1.14 mmol) and O-(2-vinyloxy-ethyl)-hydroxylamine (52 mg, 0.50 mmol) in THF (2.5 mL) was stirred at room temperature for 18 hours. The reaction mixture was partitioned between DCM (20 mL) and saturated aqueous NaHCO3. The organic layer was isolated then washed with water (20 mL), followed by brine (20 mL), dried (MgSO4), filtered and concentrated in vacuo. The resultant gum was subjected to flash chromatography (Si-PPC, gradient 0% to 100%, ethyl actetate in cyclohexane) to afford the title compound as a brown gum (149 mg, 80%). LCMS (method B): RT=3.49 min, [M+H]+=411.

Workup

  1. customThe reaction mixture was partitioned between DCM (20 mL) and saturated aqueous NaHCO3
  2. customThe organic layer was isolated
  3. washthen washed with water (20 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-36e6f6118f24472f922bbfe3825b7a2a
Source dataset
uspto-grants-2012_10
Patent number
US08293763B2

Reaction notes

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