Hydrochloric Acid → HCID 117942722, compound

HRID 1499187Notes

Reaction equation

HRID 1499187 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH:15]([C:16]([OH:18])=[O:17])[CH2:14][C:13]2([CH2:23][CH2:22][N:21]([C:24]3[CH:29]=[C:28]([O:30][C@H:31]([C:36]4[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][C:37]=4[N:43]4[CH:47]=[CH:46][C:45]([CH3:48])=[N:44]4)[C:32]([F:35])([F:34])[F:33])[N:27]=[C:26](S(C)(=O)=O)[N:25]=3)[CH2:20][CH2:19]2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:53]1([OH:59])[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1.C([O-])([O-])=O.[Cs+].[Cs+].Cl>O1CCOCC1.O>[CH2:1]([O:8][C:9]([N:11]1[CH:15]([C:16]([OH:18])=[O:17])[CH2:14][C:13]2([CH2:23][CH2:22][N:21]([C:24]3[CH:29]=[C:28]([O:30][C@H:31]([C:36]4[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][C:37]=4[N:43]4[CH:47]=[CH:46][C:45]([CH3:48])=[N:44]4)[C:32]([F:35])([F:34])[F:33])[N:27]=[C:26]([O:59][C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=4)[N:25]=3)[CH2:20][CH2:19]2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 996PhenolHCID 10796Cesium carbonateHCID 117942124HCID 117942124, compound

Product 1

HCID 117942722HCID 117942722, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 2-((benzyloxy)carbonyl)-8-(6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)-2-(methylsulfonyl)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid (300 mg, 0.393 mmol) in 1,4-dioxane (10 mL) was added phenol (74 mg, 0.79 mmol), Cs2CO3 (512 mg, 1.5 mmol), and the reaction was heated to 70° C. for 21 h. The reaction was then cooled to RT, diluted with water, acidified to pH<1 with 1 N HCl, and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. Purification on a 50 g Isco Gold RediSep reverse phase silica cartridge (H2O:HOAc: 99:1 MeOH:HOAc 99:1) provided 2-((benzyloxy)carbonyl)-8-(6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)-2-phenoxypyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid as an off-white solid.

Workup

  1. temperatureThe reaction was then cooled to RT
  2. extractionextracted with EtOAc
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification on a 50 g Isco Gold RediSep reverse phase silica cartridge (H2O:HOAc: 99:1 MeOH:HOAc 99:1)

Sources & evidence

ORD record
ord-c1f7e7901bd7488d9dba7984435d1715
Source dataset
uspto-grants-2015_12
Patent number
US09199994B2

Reaction notes

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