Diisopropylethylamine → HCID 16039687, compound

HRID 1175903Notes

Reaction equation

HRID 1175903 reaction equation
CN(C(ON1N=NC2C=[CH:13][CH:14]=[N:15][C:10]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:25]([N:27]1[CH:31]=[CH:30][C:29]([NH:32][C:33]([C:35]2[CH:36]=[C:37]([O:47][C:48]3[N:49]=[CH:50][C:51]([C:54]([OH:56])=O)=[N:52][CH:53]=3)[CH:38]=[C:39]([O:41][C@@H:42]([CH3:46])[CH2:43][O:44][CH3:45])[CH:40]=2)=[O:34])=[N:28]1)[CH3:26].Cl.N1CCC1.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[N:15]1([C:54]([C:51]2[N:52]=[CH:53][C:48]([O:47][C:37]3[CH:36]=[C:35]([CH:40]=[C:39]([O:41][C@@H:42]([CH3:46])[CH2:43][O:44][CH3:45])[CH:38]=3)[C:33]([NH:32][C:29]3[CH:30]=[CH:31][N:27]([CH2:25][CH3:26])[N:28]=3)=[O:34])=[N:49][CH:50]=2)=[O:56])[CH2:14][CH2:13][CH2:10]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 12308726Azetidine hydrochlorideHCID 53629646HCID 53629646, compound

Product 1

HCID 16039687HCID 16039687, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

HATU (304 mg, 0.80 mmol) was added to 5-[(3-{[(1-ethyl-1H-pyrazol-3-yl)amino]carbonyl}-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}phenyl)oxy]pyrazine-2-carboxylic acid (0.4 mmol) and azetidine hydrochloride (75 mg, 0.89 mmol) in DMF (5 mL) followed by addition of DIPEA (0.278 mL, 1.6 mmol) and the reaction was stirred for 16 hours. The reaction mixture was added to ethyl acetate (20 mL), the organic solution washed with water (10 mL), 2N citric acid (10 mL), saturated aqueous sodium hydrogencarbonate (10 mL) and brine (10 mL), then dried (MgSO4), filtered and evaporated under reduced pressure to a gum. The residue was purified by chromatography on silica, eluting with 70-100% ethyl acetate in hexane, to give the desired compound as a white foam (98 mg). 1H NMR δ (CDCl3): 1.27 (d, 3H), 1.40 (t, 3H), 2.31 (quin, 2H), 3.34 (s, 3H), 3.43-3.54 (m, 2H), 4.01 (q, 2H), 4.19 (t, 2H), 4.54 (q, 1H), 4.62 (t, 2H), 6.73 (d, 1H), 6.87 (t, 1H), 7.18 (t, 1H), 7.27 (d, 1H), 7.30 (t, 1H), 8.26 (d, 1H), 8.49 (s, 1H), 8.78 (d, 1H); m/z 481 (M+H)+

Workup

  1. washthe organic solution washed with water (10 mL), 2N citric acid (10 mL), saturated aqueous sodium hydrogencarbonate (10 mL) and brine (10 mL)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. customevaporated under reduced pressure to a gum
  5. customThe residue was purified by chromatography on silica
  6. washeluting with 70-100% ethyl acetate in hexane

Sources & evidence

ORD record
ord-412002fb7613413cb382fdee93cd2769
Source dataset
uspto-grants-2010_11
Patent number
US07842694B2

Reaction notes

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