Hydrochloric Acid → HCID 76285608, compound

HRID 1050305Notes

Reaction equation

HRID 1050305 reaction equation
[CH2:1]([O:8][C@H:9]1[CH2:13][N:12]([C:14]([O:16]C(C)(C)C)=O)[C@H:11]([CH2:21]O)[CH2:10]1)[C:2]1C=CC=CC=1.Cl.O1CCOCC1.[OH:30][CH:31]([C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([C:41]([F:44])([F:43])[F:42])[CH:36]=1)[C:32]([OH:34])=O.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)[C:56]2[N:57]=[CH:58][CH:59]=[CH:60][C:55]=2[N:54]=N1.C[N:70]1CCO[CH2:72][CH2:71]1>CO>[CH:60]1([C:55]2[N:54]=[CH:2][C:1]([O:8][C@H:9]3[CH2:13][N:12]4[C:14](=[O:16])[CH2:72][CH2:71][N:70]([C:32](=[O:34])[CH:31]([OH:30])[C:35]5[CH:40]=[CH:39][CH:38]=[C:37]([C:41]([F:44])([F:43])[F:42])[CH:36]=5)[CH2:21][C@@H:11]4[CH2:10]3)=[N:57][CH:56]=2)[CH2:59][CH2:58]1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 312751,4-DioxaneHCID 101658Hydroxy[3-(trifluoromethyl)phenyl]acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 14821719HCID 14821719, compound

Product 1

HCID 76285608HCID 76285608, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of the product from Example 28, Part F (90 mg, 0.232 mmol) in anhydrous methanol (3 mL) was added 4 M HCl in 1,4-dioxane (0.579 mL, 2.317 mmol). The resulting mixture was stirred at room temperature for 18 hours, and the volatiles were removed in vacuo. The residue was suspended in N,N-dimethylformamide (3 mL), 2-hydroxy-2-(3-(trifluoromethyl)phenyl)acetic acid (0.056 g, 0.255 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 0.106 g, 0.278 mmol), and N-methyl morpholine (0.117 g, 1.158 mmol) were added, and the resulting solution was stirred at room temperature for 16 hours. The mixture was partitioned between water and ethyl acetate. The organic extract was washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using a solvent gradient of 0-7% methanol in dichloromethane. The title compound was obtained as a colorless solid (0.065 g, 57% yield). 1H NMR (400 MHz, pyridine-d5, 90° C.) δ ppm 8.09-7.99 (m, 2H), 7.98 (d, J=1.4 Hz, 1H), 7.87-7.79 (m, 1H), 7.56 (d, J=1.3 Hz, 1H), 7.43 (t, J=7.8 Hz, 1H), 5.94-5.85 (m, 1H), 5.40 (t, J=4.1 Hz, 1H), 4.90-4.15 (m, 3H), 4.12 (d, J=13.5 Hz, 1H), 3.73 (dd, J=13.5, 4.3 Hz, 1H), 3.50-2.15 (m, 6H), 2.07-1.79 (m, 2H), 1.05-0.93 (m, 2H), 0.95-0.83 (m, 2H).); MS (ESI) m/z 491 (M+H)+.

Workup

  1. customthe volatiles were removed in vacuo
  2. stirringthe resulting solution was stirred at room temperature for 16 hours
  3. customThe mixture was partitioned between water and ethyl acetate
  4. extractionThe organic extract
  5. washwas washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by column chromatography on silica gel using a solvent gradient of 0-7% methanol in dichloromethane

Sources & evidence

ORD record
ord-2eb04ec10f154366a922e13991cc270d
Source dataset
uspto-grants-2016_07
Patent number
US09382258B2

Reaction notes

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