Potassium Hydroxide → HCID 67775899, compound

HRID 1808837Notes

Reaction equation

HRID 1808837 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:25][C:26]1[CH:34]=[CH:33][C:29]([C:30]([OH:32])=O)=[CH:28][C:27]=1[CH3:35].CCN(C(C)C)C(C)C.[CH3:45][C@:46]([NH:56][CH3:57])([CH:53]([CH3:55])[CH3:54])[CH2:47][N:48]1[CH2:51][CH:50]([OH:52])[CH2:49]1.[OH-].[K+]>CN(C=O)C.C(Cl)Cl.CO>[F:25][C:26]1[CH:34]=[CH:33][C:29]([C:30]([N:56]([C@@:46]([CH3:45])([CH:53]([CH3:54])[CH3:55])[CH2:47][N:48]2[CH2:49][CH:50]([OH:52])[CH2:51]2)[CH3:57])=[O:32])=[CH:28][C:27]=1[CH3:35]

Participants

9

Reactant 5

HCID 14797Potassium HydroxideHCID 81531DiisopropylethylamineHCID 2428284-Fluoro-3-methylbenzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67773354HCID 67773354, compound2×

Product 1

HCID 67775899HCID 67775899, compoundYield 0.6%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

HATU (0.408 g, 1.07 mmol) was added to a mixture of 4-fluoro-3-methylbenzoic acid (5.34 ml, 1.07 mmol) and DIPEA (2 mL, 11.45 mmol) in DMF (10 mL). After 10 min was (S)-1-(2,3-dimethyl-2-(methylamino)butyl)azetidin-3-ol (Compound Y) (0.1 g, 0.54 mmol) in DCM added. The resultant mixture was stirred at rt over night. The mixture was concentrated and the residue dissolved in DCM. The organic phase was washed with NaHCO3 (saturated) and brine. The filtrate was dried (Na2SO4) and concentrated under reduced pressure. MeOH (10 mL) and KOH (2.221 ml, 3.22 mmol) was added and the resultant mixture was stirred at rt for 3 days. The solvent was removed and the residue was purified by preparative HPLC to give the title compound (1.1 mg, 0.5%). Mixture of rotamers: 1H NMR (400 MHz, CDCl3) δ 0.91, 1.01, 2.29, 2.34-2.43, 2.81, 2.96, 3.03-3.56, 3.65-3.79, 3.79-3.96, 4.00-4.12, 4.28, 4.43-4.57, 6.92-7.06, 7.16-7.25. Total no of protons: 27. HRMS (M+H)+: calculated 323.2135. found 323.2113.

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutionthe residue dissolved in DCM
  3. washThe organic phase was washed with NaHCO3 (saturated) and brine
  4. dry with materialThe filtrate was dried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe solvent was removed
  7. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-24f12d3dff674a65ad58c85073934790
Source dataset
uspto-grants-2013_01
Patent number
US08361998B2

Reaction notes

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