Sodium Chloride → HCID 178501946, compound

HRID 516214Notes

Reaction equation

HRID 516214 reaction equation
[Cl:1][C:2]1[C:3]([F:49])=[C:4]([CH:9]2[O:14][C:13](=[O:15])[N:12]([C@@H:16]3[C:32]4=[N:33][C:29](=[CH:30][N:31]4COCC[Si](C)(C)C)[C:28]4[C:23](=[CH:24][C:25]([NH:42][C:43](=[O:46])[O:44][CH3:45])=[CH:26][CH:27]=4)[NH:22][C:21](=[O:47])[C@H:20]([CH3:48])[CH2:19][CH2:18][CH2:17]3)[CH2:11][CH2:10]2)[C:5]([F:8])=[CH:6][CH:7]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[Cl-].[Na+]>O1CCOCC1.CN(C1C=CN=CC=1)C.CCOC(C)=O>[Cl:1][C:2]1[C:3]([F:49])=[C:4]([C@@H:9]2[O:14][C:13](=[O:15])[N:12]([C@@H:16]3[C:32]4=[N:33][C:29](=[CH:30][NH:31]4)[C:28]4[C:23](=[CH:24][C:25]([NH:42][C:43](=[O:46])[O:44][CH3:45])=[CH:26][CH:27]=4)[NH:22][C:21](=[O:47])[C@H:20]([CH3:48])[CH2:19][CH2:18][CH2:17]3)[CH2:11][CH2:10]2)[C:5]([F:8])=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 5234Sodium ChlorideHCID 682631,1'-CarbonyldiimidazoleHCID 86721105HCID 86721105, compound

Product 1

HCID 178501946HCID 178501946, compoundYield 55%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Methyl N-[(10R,14S)-14-[6-(3-chloro-2,6-difluorophenyl)-2-oxo-1,3-oxazinan-3-yl]-10-methyl-9-oxo-16-{[2-(trimethylsilyl)ethoxy]methyl}-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2,4,6,15(18)-pentaen-5-yl]carbamate: To a solution of 10G (26 mg, 0.038 mmol) in dioxane (2 mL) was added CDI (60.9 mg, 0.376 mmol), TEA (0.262 mL, 1.878 mmol), DMAP (7.4 mg, 0.061 mmol) and sodium chloride (10.97 mg, 0.188 mmol). The reaction mixture was stirred at rt for 15 min. After 15 min, the reaction mixture was heated at 60° C. for 15 h. Aliquot LCMS shows the reaction mixture still contained the starting material and so the reaction mixture was heated at 70° C. for another 8 h. The reaction mixture was then cooled down to rt and diluted with EtOAc. The EtOAc layers were washed with water followed by brine and dried over MgSO4. The organic layers were concentrated and purified by silica gel chromatography. Desired fractions were pooled together and concentrated to yield the desired product (15 mg, 55%) as white solid product. MS (ESI) m/z: 718.1 (M+H)+.

Workup

  1. waitAfter 15 min
  2. temperaturethe reaction mixture was heated at 60° C. for 15 h
  3. temperatureso the reaction mixture was heated at 70° C. for another 8 h
  4. temperatureThe reaction mixture was then cooled down to rt
  5. washThe EtOAc layers were washed with water
  6. dry with materialdried over MgSO4
  7. concentrationThe organic layers were concentrated
  8. custompurified by silica gel chromatography
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-c810bd39d5e244caa5d0ef21c56f3f8a
Source dataset
uspto-grants-2015_08
Patent number
US09108981B2

Reaction notes

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