Hydrochloric Acid → HCID 67040214, compound

HRID 883943Notes

Reaction equation

HRID 883943 reaction equation
C1C2C(COC(=O)[NH:17][C:18]3[CH:23]=[CH:22][C:21]([S:24][C:25]4[CH:30]=[CH:29][C:28]([C:31](=[O:40])[NH:32][C:33]5[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][N:34]=5)=[CH:27][C:26]=4[NH:41][C:42]4[C:43]5[CH:51]=[CH:50][C:49]([CH:52]([CH3:54])[CH3:53])=[N:48][C:44]=5[N:45]=[CH:46][N:47]=4)=[CH:20][CH:19]=3)C3C(=CC=CC=3)C=2C=CC=1.O.[OH-].[Li+].Cl>O1CCOCC1.O.C(OCC)(=O)C>[NH2:17][C:18]1[CH:23]=[CH:22][C:21]([S:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]([NH:32][C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][N:34]=3)=[O:40])=[CH:27][C:26]=2[NH:41][C:42]2[C:43]3[CH:51]=[CH:50][C:49]([CH:52]([CH3:54])[CH3:53])=[N:48][C:44]=3[N:45]=[CH:46][N:47]=2)=[CH:20][CH:19]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 67040097HCID 67040097, compound

Product 1

HCID 67040214HCID 67040214, compoundYield 71%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of the product of Example 52F (167 mg, 0.2185 mmol) in 1,4-dioxane (4 mL) was treated with a solution of lithium hydroxide monohydrate (18.3 mg, 0.437 mmol) in water (2 mL) at ambient temperature, then heated at 60° for 40 minutes. The reaction was cooled to room temperature, diluted with ethyl acetate (100 mL) and water (30 mL), adjusted the aqueous pH to 6 with 1N aqueous hydrochloric acid, and separated the layers. The organic phase was washed with water (2×25 mL) and brine (25 mL), dried over anhydrous sodium sulfate, filtered, and concentrated by rotary evaporation in vacuo. Purification of the residue by silica gel flash chromatography with 5% methanol/methylene chloride afforded the title compound as a yellow solid (84 mg, 71%). 1H NMR (300 MHz, DMSO-D6) δ ppm: 1.34 (d, J=6.99 Hz, 6 H) 3.15-3.30 (m, 1 H) 5.62 (s, 2 H) 6.65 (d, J=8.46 Hz, 2 H) 6.77-6.89 (m, 1 H) 7.15 (d, J=8.46 Hz, 2 H) 7.64 (d, J=8.09 Hz, 1 H) 7.87 (d, J=8.46 Hz, 1 H) 7.95 (dd, J=8.82, 2.57 Hz, 1 H) 8.04 (s, 1 H) 8.21 (d, J=9.19 Hz, 1 H) 8.42 (d, J=2.57 Hz, 1 H) 8.58 (s, 1 H) 8.89 (d, J=8.46 Hz, 1 H) 10.13 (s, 1 H) 10.92 (s, 1 H); MS (ESI+) m/z 542/544 (M+H)+.

Workup

  1. temperatureheated at 60° for 40 minutes
  2. customseparated the layers
  3. washThe organic phase was washed with water (2×25 mL) and brine (25 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation in vacuo
  7. customPurification of the residue by silica gel flash chromatography with 5% methanol/methylene chloride

Sources & evidence

ORD record
ord-b8e5f3aa05304695bb4d68dec0687bc7
Source dataset
uspto-grants-2012_08
Patent number
US08236950B2

Reaction notes

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