Diisopropylethylamine → HCID 68380152, compound

HRID 2178695Notes

Reaction equation

HRID 2178695 reaction equation
[CH3:1][C:2]1[N:3]=[CH:4][N:5]([C:7]2[C:12](=[O:13])[NH:11][C:10]([C:14]([OH:16])=O)=[CH:9][CH:8]=2)[CH:6]=1.[F:17][C:18]1[CH:30]=[CH:29][C:21]([O:22][CH2:23][CH2:24][NH:25][CH2:26][CH2:27]O)=[C:20]([C:31]([F:34])([F:33])[F:32])[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>O.ClCCl>[F:17][C:18]1[CH:30]=[CH:29][C:21]([O:22][CH2:23][CH2:24][N:25]2[CH2:26][CH2:27][N:11]3[C:12](=[O:13])[C:7]([N:5]4[CH:6]=[C:2]([CH3:1])[N:3]=[CH:4]4)=[CH:8][CH:9]=[C:10]3[C:14]2=[O:16])=[C:20]([C:31]([F:32])([F:33])[F:34])[CH:19]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66551970HCID 66551970, compoundHCID 68380331HCID 68380331, compound

Product 1

HCID 68380152HCID 68380152, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

5-(4-Methyl-1H-imidazol-1-yl)-6-oxo-1,6-dihydropyridine-2-carboxylic acid, 0.7 hydrobromide salt (P1) (201 mg, 0.729 mmol) and 2-({2-[4-fluoro-2-(trifluoromethyl)phenoxy]ethyl}amino)ethanol (C36) (214 mg, 0.801 mmol) were combined with dichloromethane (15 mL) and N,N-diisopropylethylamine (0.508 mL, 2.92 mmol), and the mixture was stirred for 5 minutes at room temperature. O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 97%, 857 mg, 2.19 mmol) was added in one portion, and the reaction was stirred for an additional 16 hours. Water (50 mL) was added, and the mixture was extracted with dichloromethane (3×50 mL). The combined organic layers were washed sequentially with saturated aqueous sodium bicarbonate solution (50 mL), water (50 mL) and saturated aqueous sodium chloride solution (50 mL), then dried over magnesium sulfate and concentrated in vacuo. Purification was carried out twice using silica gel chromatography (Gradient #1: 0% to 20% methanol in dichloromethane; Gradient #2: 0% to 70% [10% 2 N ammonia in methanol/90% ethyl acetate] in ethyl acetate) to afford the title compound as a white solid. Yield: 268 mg, 0.595 mmol, 82%. LCMS m/z 451.0 (M+1). 1H NMR (400 MHz, CD3OD) δ 2.24 (d, J=0.9 Hz, 3H), 3.90-3.95 (m, 2H), 4.01 (dd, J=5.1, 5.1 Hz, 2H), 4.32-4.37 (m, 4H), 7.21-7.26 (m, 1H), 7.25 (d, J=7.8 Hz, 1H), 7.30-7.32 (m, 1H), 7.32-7.39 (m, 2H), 7.76 (d, J=7.8 Hz, 1H), 8.30 (d, J=1.3 Hz, 1H).

Workup

  1. stirringthe reaction was stirred for an additional 16 hours
  2. extractionthe mixture was extracted with dichloromethane (3×50 mL)
  3. washThe combined organic layers were washed sequentially with saturated aqueous sodium bicarbonate solution (50 mL), water (50 mL) and saturated aqueous sodium chloride solution (50 mL)
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customPurification

Sources & evidence

ORD record
ord-9217029b4f2e4db7acd576bdcec6728b
Source dataset
uspto-grants-2015_06
Patent number
US09067934B2

Reaction notes

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