1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 44137225, compound

HRID 2067021Notes

Reaction equation

HRID 2067021 reaction equation
[CH:1]1([C:4]2[CH:9]=[CH:8][C:7]([NH:10][C:11]3[C:12]4[N:13]([CH:20]=[N:21][CH:22]=4)[CH:14]=[CH:15][C:16]=3[C:17]([OH:19])=O)=[C:6]([F:23])[CH:5]=2)[CH2:3][CH2:2]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.[NH2:55][O:56][CH2:57][C@@H:58]([OH:60])[CH3:59]>CN(C=O)C>[OH:60][C@@H:58]([CH3:59])[CH2:57][O:56][NH:55][C:17]([C:16]1[CH:15]=[CH:14][N:13]2[CH:20]=[N:21][CH:22]=[C:12]2[C:11]=1[NH:10][C:7]1[CH:8]=[CH:9][C:4]([CH:1]2[CH2:2][CH2:3]2)=[CH:5][C:6]=1[F:23])=[O:19]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 595651948-(4-Cyclopropyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acidHCID 86637725(S)-1-aminooxypropan-2-ol hydrochloride

Product 1

HCID 44137225HCID 44137225, compoundYield 28.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of 8-(4-cyclopropyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (0.11 g, 0.35 mmol), EDCI (0.081 g, 0.42 mmol), HOBt (0.057 g, 0.42 mmol), DIPEA (0.085 mL, 0.88 mmol) and (S)-1-aminooxy-propan-2-ol hydrochloride (0.05 g, 0.39 mmol) in DMF (1.5 mL) was stirred at room temperature for 18 hours. The reaction mixture was partitioned between DCM (5 mL) and saturated aqueous NaHCO3 (5 mL). The organic layer was washed with water (5 mL), followed by brine (5 mL), then dried (MgSO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0% to 60%, ethyl actetate in DCM) to give a yellow sticky solid, which was further purified by preparative HPLC (Gemini 5 micron C18 250×21.20 mm column, 0.1% formic acid, gradient acetonitrile/water, 5 to 98%, ramp time 20 minutes) to afford the title compound as a yellow solid (38 mg, 27%). LCMS (method A): RT=6.87 min, [M+H]+=385. 1H NMR (DMSO-d6) 10.54 (1H, s), 8.27 (1 H, s), 7.76 (1H, dd, J=7.37, 0.93 Hz), 7.14 (1H, t, J=8.37 Hz), 6.98 (1H, dd, J=11.87, 1.95 Hz), 6.95-6.89 (1H, m), 6.76 (1H, d, J=7.33 Hz), 6.27 (1H, s), 3.89-3.79 (1H, m), 3.72-3.62 (2H, m), 1.99-1.90 (1H, m), 1.04 (3H, d, J=6.34 Hz), 0.99-0.93 (2H, m), 0.76-0.67 (2H, m).

Workup

  1. customThe reaction mixture was partitioned between DCM (5 mL) and saturated aqueous NaHCO3 (5 mL)
  2. washThe organic layer was washed with water (5 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a yellow sticky solid, which
  7. customwas further purified by preparative HPLC (Gemini 5 micron C18 250×21.20 mm column, 0.1% formic acid, gradient acetonitrile/water, 5 to 98%, ramp time 20 minutes)

Sources & evidence

ORD record
ord-1e01a86a02c44e0c80c40ac4a2b38504
Source dataset
uspto-grants-2012_10
Patent number
US08293763B2

Reaction notes

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