Triethylamine → HCID 178480283, compound

HRID 1931088Notes

Reaction equation

HRID 1931088 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[NH:6]1[CH2:9][CH:8]([CH2:10][O:11][C:12]2[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][C:13]=2[C:14](/[N:16]=[C:17]2/[N:18]([CH2:27][C@H:28]3[CH2:32][CH2:31][CH2:30][O:29]3)[N:19]([CH3:26])[C:20]([C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:21]/2)=[O:15])[CH2:7]1.C(N(CC)CC)C>C1COCC1>[C:22]([C:20]1[N:19]([CH3:26])[N:18]([CH2:27][C@H:28]2[CH2:32][CH2:31][CH2:30][O:29]2)/[C:17](=[N:16]/[C:14](=[O:15])[C:13]2[CH:33]=[C:34]([C:37]([F:40])([F:39])[F:38])[CH:35]=[CH:36][C:12]=2[O:11][CH2:10][CH:8]2[CH2:9][N:6]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:7]2)/[CH:21]=1)([CH3:25])([CH3:23])[CH3:24]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 178480282HCID 178480282, compound

Product 1

HCID 178480283HCID 178480283, compoundYield 52.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methanesulfonyl chloride (0.05 g, 0.4 mmol) was added to a solution of Example 54B (0.21 g, 0.4 mmol) in THF (5.0 mL) followed by triethylamine (0.17 mL, 1.2 mmol). The mixture was stirred for 1 hour at ambient temperature, then partitioned between EtOAc (15 mL) and saturated NaHCO3 (1 mL). The organic extract was washed with water and brine, dried with MgSO4, filtered and concentrated. The residue was purified by chromatography (SiO2, solvent A-hexane:EtOAc:Et3N (1:3:0.2), solvent B-hexane:EtOAc:MeOH:Et3N (1:3:1:0.2) 100% solvent A to 100% solvent B over 450 mL then isocratic for 180 mL) to afford the title compound (0.12 g, 0.21 mmol, 49% yield). 1H NMR (500 MHz, pyridine-d5) δ ppm 1.21 (s, 9H), 1.54-1.62 (m, 2H), 1.64-1.71 (m, 1H), 1.75-1.85 (m, 1H), 3.01-3.09 (m, 1H), 3.31 (s, 3H), 3.54-3.63 (m, 1H), 3.69-3.76 (m, 1H), 3.85 (s, 3H), 4.05 (t, J=8.1 Hz, 2H), 4.09 (d, J=4.3 Hz, 2H), 4.22-4.28 (m, 1H), 4.36-4.46 (m, 3H), 4.62 (dd, J=15.1, 3.2 Hz, 1H), 7.12 (d, J=8.8 Hz, 1H), 7.46 (s, 1H), 7.65 (dd, J=8.7, 2.3 Hz, 1H), 8.48 (d, J=2.4 Hz, 1H); MS (ESI+) m/z 573.2 [M+H]+.

Workup

  1. custompartitioned between EtOAc (15 mL) and saturated NaHCO3 (1 mL)
  2. extractionThe organic extract
  3. washwas washed with water and brine
  4. dry with materialdried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography (SiO2, solvent A-hexane:EtOAc:Et3N (1:3:0.2), solvent B-hexane:EtOAc:MeOH:Et3N (1:3:1:0.2) 100% solvent A to 100% solvent B over 450 mL

Sources & evidence

ORD record
ord-3990fa2c83aa4398b08fc05f8dfac0bb
Source dataset
uspto-grants-2012_05
Patent number
US08188135B2

Reaction notes

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