Diisopropylethylamine → HCID 67542725, compound

HRID 219971Notes

Reaction equation

HRID 219971 reaction equation
[CH3:1][O:2][CH2:3][C:4]1[CH:9]=[C:8]([C:10]([OH:12])=O)[CH:7]=[CH:6][C:5]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[O:53]1[CH2:57][CH2:56][O:55][CH:54]1[C:58]1[CH:59]=[C:60]([C:64](=[N:66]O)[NH2:65])[CH:61]=[CH:62][CH:63]=1>CN(C=O)C.CCOC(C)=O.N1C=CC=CC=1.C1(C)C=CC=CC=1>[O:53]1[CH2:57][CH2:56][O:55][CH:54]1[C:58]1[CH:59]=[C:60]([C:64]2[N:65]=[C:10]([C:8]3[CH:7]=[CH:6][C:5]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=4[CH3:19])=[C:4]([CH2:3][O:2][CH3:1])[CH:9]=3)[O:12][N:66]=2)[CH:61]=[CH:62][CH:63]=1

Participants

9

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 594958222-(Methoxymethyl)-2'-methylbiphenyl-4-carboxylic acidHCID 72307468HCID 72307468, compound

Product 1

HCID 67542725HCID 67542725, compound

Reagents, catalysts & solvents 4

HCID 1049PyridineSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of Intermediate 28 (2 973 mg; 11.60 mmol) and DIEA (3.94 mL; 23.2 mmol) in anhydrous DMF (10 mL) at 0° C. was added HATU (4 410 mg; 11.60 mmol). The reaction mixture was stirred at 0° C. for 10 min. Intermediate 68 (2 300 mg; 11.05 mmol) was added at once. The reaction mixture was stirred at 0° C. for 15 min and RT for 2 h. EtOAc was added and the organic layer was washed with water and brine (50 mL), dried (MgSO4) and the solvents were removed under reduced pressure to give an oil. The oil was taken up with toluene (70 mL) and pyridine (10 mL). The resulting mixture was heated at 110° C. overnight. EtOAc was added and the organic layer was washed with water and brine (50 mL), dried (MgSO4) and the solvents were removed under reduced pressure to give a yellow oil. The crude material was purified by flash chromatography (EtOAc/cHex) to afford the title compound as an oil. 1H NMR: (DMSO-d6, 300 MHz) δ 8.33 (m, 1H), 8.17 (m, 3H), 7.76 (m, 2H), 7.43 (d, J=7.9 Hz, 1H), 7.38-7.25 (m, 3H), 7.16 (m, 1H), 5.90 (s, 1H), 4.23 (d, J=12.9 Hz, 1H), 4.17 (d, J=12.9 Hz, 1H), 4.15-3.98 (m, 4H), 3.25 (s, 3H), 2.31 (t, J=7.40 Hz, 2H), 2.04 (s, 3H). LC/MS (Method B): 429.2 (M+H)+ no (M−H)−. HPLC (Method A) Rt: 5.53 min (purity: 89.8%).

Workup

  1. stirringThe reaction mixture was stirred at 0° C. for 15 min and RT for 2 h
  2. washthe organic layer was washed with water and brine (50 mL)
  3. dry with materialdried (MgSO4)
  4. customthe solvents were removed under reduced pressure
  5. customto give an oil
  6. temperatureThe resulting mixture was heated at 110° C. overnight
  7. washthe organic layer was washed with water and brine (50 mL)
  8. dry with materialdried (MgSO4)
  9. customthe solvents were removed under reduced pressure
  10. customto give a yellow oil
  11. customThe crude material was purified by flash chromatography (EtOAc/cHex)

Sources & evidence

ORD record
ord-d2d348b4891f4ab7b87874c42bc28e0d
Source dataset
uspto-grants-2012_06
Patent number
US08202865B2

Reaction notes

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