Diisopropylethylamine → HCID 68380401, compound

HRID 2364976Notes

Reaction equation

HRID 2364976 reaction equation
[CH3:1][C:2]1[O:3][C:4]([C:7]2[C:12](=[O:13])[NH:11][C:10]([C:14]([OH:16])=O)=[CH:9][CH:8]=2)=[CH:5][N:6]=1.[F:17][C:18]1[CH:27]=[C:26]2[C:21]([CH:22]=[CH:23][CH:24]=[C:25]2[O:28][CH2:29][CH2:30][NH:31][CH2:32][CH2:33]O)=[CH:20][CH:19]=1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(=O)(O)[O-].[Na+]>ClCCl>[F:17][C:18]1[CH:27]=[C:26]2[C:21]([CH:22]=[CH:23][CH:24]=[C:25]2[O:28][CH2:29][CH2:30][N:31]2[CH2:32][CH2:33][N:11]3[C:12](=[O:13])[C:7]([C:4]4[O:3][C:2]([CH3:1])=[N:6][CH:5]=4)=[CH:8][CH:9]=[C:10]3[C:14]2=[O:16])=[CH:20][CH:19]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68380172HCID 68380172, compoundHCID 68380198HCID 68380198, compound

Product 1

HCID 68380401HCID 68380401, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-(2-Methyl-1,3-oxazol-5-yl)-6-oxo-1,6-dihydropyridine-2-carboxylic acid (C39) (45 mg, 0.20 mmol) and 2-({2-[(7-fluoronaphthalen-1-yl)oxy]ethyl}amino)ethanol (C41) (55.8 mg, 1.1 mmol) were combined with dichloromethane (4 mL) and N,N-diisopropylethylamine (178 μL, 1.02 mmol). O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 97%, 171 mg, 0.45 mmol) was added, and the reaction was stirred at room temperature for 18 hours. Saturated aqueous sodium bicarbonate solution was added and the mixture was extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. Purification via silica gel chromatography (Gradient: 50% to 100% ethyl acetate in heptane, followed by elution with 20% methanol in ethyl acetate) was followed by high-pressure liquid chromatographic purification (Silica column, 5 μm; Gradient: 5% to 100% ethanol in heptane), to afford the title compound as a solid. Yield: 10 mg, 0.022 mmol, 11%. LCMS m/z 434.5 (M+1). 1H NMR (400 MHz, CDCl3) δ 2.64 (s, 3H), 3.97-4.02 (m, 2H), 4.12-4.16 (m, 2H), 4.39-4.47 (m, 4H), 6.85 (d, J=7.6 Hz, 1H), 7.26-7.31 (m, 1H, assumed; partially obscured by solvent peak), 7.31-7.36 (m, 2H), 7.46 (d, J=8.2 Hz, 1H), 7.71 (dd, J=10.3, 2.5 Hz, 1H), 7.81 (dd, J=9.0, 5.5 Hz, 1H), 7.89 (d, J=7.6 Hz, 1H), 8.00 (s, 1H).

Workup

  1. extractionthe mixture was extracted three times with ethyl acetate
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customPurification
  5. washvia silica gel chromatography (Gradient: 50% to 100% ethyl acetate in heptane, followed by elution with 20% methanol in ethyl acetate)
  6. customwas followed by high-pressure liquid chromatographic purification (Silica column, 5 μm; Gradient: 5% to 100% ethanol in heptane)

Sources & evidence

ORD record
ord-26d2ec76011c4685959a237aedd2b9c5
Source dataset
uspto-grants-2014_04
Patent number
US08697673B2

Reaction notes

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