Morpholine → HCID 16040147, compound

HRID 1989916Notes

Reaction equation

HRID 1989916 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:36]([OH:38])=O)[CH:5]=[N:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([C:15]([NH:17][C:18]2[CH:22]=[CH:21][N:20]([CH3:23])[N:19]=2)=[O:16])[CH:12]=[C:11]([O:24][C@@H:25]([CH3:35])[CH2:26][O:27][Si](C(C)(C)C)(C)C)[CH:10]=1.[NH:39]1[CH2:44][CH2:43][O: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>CN(C=O)C.O>[Cl:1][C:2]1[C:7]([O:8][C:9]2[CH:14]=[C:13]([CH:12]=[C:11]([O:24][C@@H:25]([CH3:35])[CH2:26][OH:27])[CH:10]=2)[C:15]([NH:17][C:18]2[CH:22]=[CH:21][N:20]([CH3:23])[N:19]=2)=[O:16])=[N:6][CH:5]=[C:4]([C:36]([N:39]2[CH2:44][CH2:43][O:42][CH2:41][CH2:40]2)=[O:38])[CH:3]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 53629635HCID 53629635, compound

Product 1

HCID 16040147HCID 16040147, compoundYield 24.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution 5-chloro-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 (0.15 g, 0.267 mmol), morpholine (0.07 mL, 0.803 mmol), HATU (0.213 g, 0.560 mmol) and DIPEA (0.15 mL, 0.861 mmol) in DMF (7 mL) was stirred at RT for 2 days. Water (20 mL) was added and the solution extracted with ethyl acetate (50 mL). The ethyl acetate layer was separated, washed with brine and dried (MgSO4), and evaporated to a residue which was chromatographed on silica, eluting with 1% methanol in ethyl acetate. 3.5M Hydrochloric acid (0.5 mL) was added to a solution of the residual solid taken up in methanol (5 mL) and allowed to stir at RT for 20 minutes. The solution was neutralised with saturated sodium bicarbonate solution and the methanol removed in vaccuo and the residual solution partitioned between water (20 mL) and ethyl acetate. The ethyl acetate layer was separated and washed with brine, dried (MgSO4) and evaporated to give the desired product (34 mg). 1H NMR δ (d6-DMSO): 1.28 (d, 3H), 3.58 (m, 10H), 3.81 (s, 3H), 4.61 (sextet, 1H), 4.89 (t, 1H), 6.60 (d, 1H), 7.03 (t, 1H), 7.41 (s, 1H), 7.54 (s, 1H), 7.63 (d, 1H), 8.20 (q, 2H), 10.84 (s, 1H). m/z 516 (M+H)+

Workup

  1. extractionthe solution extracted with ethyl acetate (50 mL)
  2. customThe ethyl acetate layer was separated
  3. washwashed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated to a residue which
  6. customwas chromatographed on silica
  7. washeluting with 1% methanol in ethyl acetate
  8. addition3.5M Hydrochloric acid (0.5 mL) was added to a solution of the residual solid
  9. customthe methanol removed in vaccuo
  10. customthe residual solution partitioned between water (20 mL) and ethyl acetate
  11. customThe ethyl acetate layer was separated
  12. washwashed with brine
  13. dry with materialdried (MgSO4)
  14. customevaporated

Sources & evidence

ORD record
ord-e853a95423a74e23adf961b7bedfa90d
Source dataset
uspto-grants-2010_01
Patent number
US07642263B2

Reaction notes

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