Water → HCID 90413864, compound

HRID 1522032Notes

Reaction equation

HRID 1522032 reaction equation
[F:1][C:2]1[C:3]([C:19]2[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=2[O:26][CH3:27])=[C:4]2[CH:10]=[C:9]([C:11]3[CH2:12][CH:13]4[CH2:17][NH:16][CH2:15][CH:14]4[CH:18]=3)[NH:8][C:5]2=[N:6][CH:7]=1.Cl[CH2:29][C:30]([N:32]([CH3:34])[CH3:33])=[O:31].C(N(CC)CC)C.O>CN(C)C=O.[Cl-].[Na+].O>[F:1][C:2]1[C:3]([C:19]2[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=2[O:26][CH3:27])=[C:4]2[CH:10]=[C:9]([C:11]3[CH2:12][CH:13]4[CH2:17][N:16]([CH2:29][C:30]([N:32]([CH3:34])[CH3:33])=[O:31])[CH2:15][CH:14]4[CH:18]=3)[NH:8][C:5]2=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 758862-chloro-N,N-dimethylacetamideHCID 90413493HCID 90413493, compound

Product 1

HCID 90413864HCID 90413864, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A mixture of Example 282A (80.0 mg, 0.182 mmol), 2-chloro-N,N-dimethylacetamide (0.021 mL, 0.209 mmol), and triethylamine (0.127 mL, 0.908 mmol) in N,N-dimethylformamide (2 mL) was heated at 75° C. for 4 hours. The mixture was treated with water and brine and extracted with ethyl acetate (twice). The combined organic layers were washed with brine, dried over magnesium sulfate, filtered, concentrated, and purified by HPLC (same protocol as Example 221). The trifluoroacetic acid salt was flushed through an SCX column eluting with 2M ammonia in methanol to give the free base of the title compound. 1H NMR (400 MHz, Pyridine-d5) δ 2.58-3.06 (m, 13H), 3.31 (d, J=5.4 Hz, 2H), 3.39-3.44 (m, 1H), 3.71 (s, 3H), 6.43 (bs, 1H), 6.48 (bs, 1H), 7.12 (dd, J=9.1, 4.5 Hz, 1H), 7.27-7.36 (m, 1H), 7.50 (d, J=8.8 Hz, 1H), 8.51 (d, J=2.6 Hz, 1H), 13.13 (bs, 1H). MS (ESI+) m/z 453.2 (M+H)+.

Workup

  1. extractionextracted with ethyl acetate (twice)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by HPLC (same protocol as Example 221)
  7. customThe trifluoroacetic acid salt was flushed through an SCX column
  8. washeluting with 2M ammonia in methanol

Sources & evidence

ORD record
ord-8d6e5ae6562843bfaeaee6430308387d
Source dataset
uspto-grants-2015_07
Patent number
US09073922B2

Reaction notes

Loading…