Hydrochloric Acid → HCID 67405999, compound

HRID 1174403Notes

Reaction equation

HRID 1174403 reaction equation
[C:1]([O:4][CH2:5][C:6]([CH3:58])([CH3:57])[C@H:7]([NH:49][C:50]([O:52][C:53](C)(C)C)=[O:51])[C:8](=[O:48])[NH:9][C@@H:10]([CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C@@H:11]([OH:40])[CH2:12][C@H:13]([CH2:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][N:35]=2)=[CH:30][CH:29]=1)[NH:14][C:15](=[O:26])[C@H:16]([C:22]([CH3:25])([CH3:24])[CH3:23])[NH:17][C:18](=[O:21])[O:19][CH3:20])(=[O:3])[CH3:2].Cl.C(N(C(C)C)CC)(C)C.ClC(OC)=O>O1CCOCC1.O>[C:1]([O:4][CH2:5][C:6]([CH3:58])([CH3:57])[C@H:7]([NH:49][C:50]([O:52][CH3:53])=[O:51])[C:8](=[O:48])[NH:9][C@@H:10]([CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C@@H:11]([OH:40])[CH2:12][C@H:13]([CH2:27][C:28]1[CH:29]=[CH:30][C:31]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][N:35]=2)=[CH:32][CH:33]=1)[NH:14][C:15](=[O:26])[C@H:16]([C:22]([CH3:24])([CH3:23])[CH3:25])[NH:17][C:18](=[O:21])[O:19][CH3:20])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 67408147HCID 67408147, compound

Product 1

HCID 67405999HCID 67405999, compoundYield 67.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of the product of Example 174F (0.030 g, 0.037 mmol) in dioxane (0.50 mL) at 0° C. was added a solution of HCl in dioxane (3.0 mL, 4 N), and the mixture was stirred at room temperature for 1 hour. The solvent was evaporated, and the residue was dissolved in tetrahydrofuran (0.40 mL) and diisopropylethylamine (0.030 mL, 0.172 mmol) and methyl chloroformate (0.0032 mL, 0.041 mmol) were added at room temperature. After 1 hour water was added and the reaction was extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel eluting with a gradient starting with dichloromethane and ending with 50% acetone in dichloromethane to give the title compound (0.019 g, 67% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.80-0.82 (m, 15 H), 1.41-1.58 (m, 2 H), 2.00 (s, 3 H), 2.54-2.57 (m, 1 H), 2.71-2.79 (m, 3 H), 3.49 (s, 3 H), 3.55 (s, 3 H), 3.61-3.73 (m, 2 H), 3.78-3.84 (m, 1 H), 4.03-4.24 (m, 3 H), 4.90 (d, J=5.5 Hz, 1 H), 6.62 (d, J=9.6 Hz, 1 H), 7.09 (d, J=9.6 Hz, 1 H), 7.10-7.21 (m, 7 H), 7.29-7.31 (m, 1 H), 7.57 (d, J=8.8 Hz, 1 H), 7.80 (d, J=9.9 Hz, 1 H), 7.85-7.89 (m, 4 H), 8.64 (m, 1 H).

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe residue was dissolved in tetrahydrofuran (0.40 mL)
  3. extractionthe reaction was extracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was chromatographed on silica gel eluting with a gradient

Sources & evidence

ORD record
ord-de0ec1920120455aa699e308ab7b149e
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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