Hydrochloric Acid → HCID 86680463, compound

HRID 240454Notes

Reaction equation

HRID 240454 reaction equation
[CH3:1][C:2]1([C:5]2[N:6]=[CH:7][C:8]([O:11][C@H:12]3[CH2:27][N:15]4[CH2:16][CH2:17][N:18](C(OC(C)(C)C)=O)[CH2:19][C@@H:14]4[CH2:13]3)=[N:9][CH:10]=2)[CH2:4][CH2:3]1.Cl.C(N(C(C)C)CC)(C)C.[F:38][C:39]([F:51])([F:50])[C:40]1[CH:41]=[C:42]([S:46](Cl)(=[O:48])=[O:47])[CH:43]=[CH:44][CH:45]=1>O1CCOCC1.C(Cl)Cl>[CH3:1][C:2]1([C:5]2[N:6]=[CH:7][C:8]([O:11][C@H:12]3[CH2:27][N:15]4[CH2:16][CH2:17][N:18]([S:46]([C:42]5[CH:43]=[CH:44][CH:45]=[C:40]([C:39]([F:38])([F:50])[F:51])[CH:41]=5)(=[O:48])=[O:47])[CH2:19][C@@H:14]4[CH2:13]3)=[N:9][CH:10]=2)[CH2:3][CH2:4]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 27332503-(Trifluoromethyl)benzenesulfonyl chlorideHCID 86680462HCID 86680462, compound

Product 1

HCID 86680463HCID 86680463, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of the product from Example 206A (28 mg, 0.075 mmol) in 1,4-dioxane (1 mL) was added a 4 M solution of hydrogen chloride in 1,4-dioxane (0.5 mL, 2.0 mmol). The resulting mixture was stirred at room temperature for 90 minutes, and the mixture was then concentrated and dried in vacuo. To the resulting colorless solid was added CH2Cl2 (0.75 mL), diisopropylethylamine (0.065 mL, 0.375 mmol) and 3-(trifluoromethyl)benzene-1-sulfonyl chloride (22.02 mg, 0.090 mmol). The resulting mixture was stirred at room temperature for 3 hours. The mixture was partitioned between water and CH2Cl2, and the organic layer was dried over Na2SO4. The drying agent was removed by filtration, and the filtrate was concentrated in vacuo. The crude product was purified by column chromatography on silica gel using a solvent gradient of 0-40% ethyl acetate in hexanes. The title compound was obtained as a colorless solid (10 mg, 28%). 1H NMR (300 MHz, CDCl3) δ ppm 0.72-0.81 (m, 2H), 1.07-1.17 (m, 2H), 1.48 (s, 3H), 1.72-1.88 (m, 1H), 1.92-2.05 (m, 1H), 2.12 (t, J=10.51 Hz, 1H), 2.33 (dd, J=9.92, 5.16 Hz, 1H), 2.38-2.63 (m, 3H), 2.94-3.07 (m, 1H), 3.65 (dd, J=10.31, 6.74 Hz, 1H), 3.72-3.82 (m, 1H), 3.86-3.98 (m, 1H), 5.23-5.35 (m, 1H), 7.70 (t, J=7.93 Hz, 1H), 7.87 (d, J=7.93 Hz, 1H), 7.96 (d, J=7.93 Hz, 1H), 8.00 (d, J=1.19 Hz, 1H), 8.01-8.04 (m, 1H), 8.05 (d, J=1.19 Hz, 1H); MS (ESI) m/z 483 (M+H)+.

Workup

  1. concentrationthe mixture was then concentrated
  2. customdried in vacuo
  3. stirringThe resulting mixture was stirred at room temperature for 3 hours
  4. customThe mixture was partitioned between water and CH2Cl2
  5. dry with materialthe organic layer was dried over Na2SO4
  6. customThe drying agent was removed by filtration
  7. concentrationthe filtrate was concentrated in vacuo
  8. customThe crude product was purified by column chromatography on silica gel using a solvent gradient of 0-40% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-d2be18d3d58c4c1b9b0a625c8cc6434f
Source dataset
uspto-grants-2014_02
Patent number
US08648074B2

Reaction notes

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