Hydrochloric Acid → HCID 53629538, compound

HRID 1990145Notes

Reaction equation

HRID 1990145 reaction equation
CC([Si](C)(C)[O:6][CH2:7][C@@H:8]([O:10][C:11]1[CH:12]=[C:13]([O:26][C:27]2[N:32]=[CH:31][C:30]([C:33](O)=[O:34])=[CH:29][CH:28]=2)[CH:14]=[C:15]([C:17]([NH:19][C:20]2[CH:24]=[CH:23][N:22]([CH3:25])[N:21]=2)=[O:18])[CH:16]=1)[CH3:9])(C)C.Cl.[NH:39]1[CH2:42][CH2:41][CH2:40]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl.C(=O)(O)[O-].[Na+]>CN(C=O)C.O>[N:39]1([C:33]([C:30]2[CH:29]=[CH:28][C:27]([O:26][C:13]3[CH:14]=[C:15]([CH:16]=[C:11]([O:10][C@@H:8]([CH3:9])[CH2:7][OH:6])[CH:12]=3)[C:17]([NH:19][C:20]3[CH:24]=[CH:23][N:22]([CH3:25])[N:21]=3)=[O:18])=[N:32][CH:31]=2)=[O:34])[CH2:42][CH2:41][CH2:40]1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 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 12308726Azetidine hydrochlorideHCID 53629631HCID 53629631, compound

Product 1

HCID 53629538HCID 53629538, compoundYield 52.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 6-[(3-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-methylethyl)oxy]-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenyl)oxy]pyridine-3-carboxylic acid (0.20 g, 0.378 mmol), azetidine hydrochloride (0.106 g, 0.114 mmol), HATU (0.302 g, 0.794 mmol) and DIPEA (0.39 mL, 0564 mmol) in DMF (7 mL) was stirred at RT overnight. 3.5M Hydrochloric acid (0.5 mL) was added and the solution left to stir for 20 minutes. The solution was neutralised with saturated sodium bicarbonate solution. Water (20 mL) was added and the solution extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with brine, dried (MgSO4), and evaporated to a residue which was chromatographed on silica, eluting with 50% ethyl acetate in isohexane, to give the desired product (27 mg). 1H NMR δ (CDCl3): 1.32 (d, 3H), 2.38 (quintet, 2H), 3.77 (m, 2H), 3.80 (s, 3H), 4.29 (d, 4H), 4.57 (sextet, 1H), 6.81 (d, 1H), 6.91 (t, 1H), 6.99 (d, 1H), 7.27 (m, 2H), 7.38 (m, 1H), 8.42 (d, 1H), 8.86 (s, 1H). m/z 452 (M+H)+

Workup

  1. waitthe solution left
  2. extractionthe solution extracted with ethyl acetate (50 mL)
  3. washThe ethyl acetate layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated to a residue which
  6. customwas chromatographed on silica
  7. washeluting with 50% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-18018fffd16841d0aa205b69315a4473
Source dataset
uspto-grants-2010_01
Patent number
US07642259B2

Reaction notes

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