Sodium Carbonate → 2-((Benzyloxy)carbonyl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid

HRID 1499255Notes

Reaction equation

HRID 1499255 reaction equation
NC1N=C([N:8]2[CH2:30][CH2:29][C:11]3([CH2:15][N:14]([C:16]([O:18][CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)=[O:17])[C@H:13]([C:26]([OH:28])=[O:27])[CH2:12]3)[CH2:10][CH2:9]2)C=C(O[C@H](C2C=CC(Br)=CC=2)C(F)(F)F)N=1.C([O-])([O-])=O.[Na+].[Na+].COC1C=C(B(O)O)C=CC=1>O1CCOCC1>[CH2:19]([O:18][C:16]([N:14]1[CH:13]([C:26]([OH:28])=[O:27])[CH2:12][C:11]2([CH2:29][CH2:30][NH:8][CH2:9][CH2:10]2)[CH2:15]1)=[O:17])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 2734370(3-Methoxyphenyl)boronic acidHCID 117942050(S)-8-(2-amino-6-((R)-1-(4-bromophenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2-((benzyloxy)carbonyl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid

Product 1

HCID 1317342572-((Benzyloxy)carbonyl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of (S)-8-(2-amino-6-((R)-1-(4-bromophenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2-((benzyloxy)carbonyl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid (80 mg, 0.12 mmol) in dioxane (1 mL)/Na2CO3 (1.0 mL, 2 M, aq) were added (3-methoxyphenyl)boronic acid (22 mg, 0.14 mmol) and Pd(dppf)2 (8 mg, 0.01 mmol). The reaction flask was degassed and refilled with argon via balloon 3 times, and the reaction mixture was refluxed for 4 h. Then the reaction was cooled to RT, concentrated in vacuo, and extracted with EtOAc. The combined organic layers were are washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. Purification by reverse phase silica gel column (H2O/NH4OH/MeOH) provided (S)-8-(2-amino-6-((S)-2,2,2-trifluoro-1-(3′-methoxy-[1,1′-biphenyl]-4-yl)ethoxy)-4-yl)ethoxy)pyrimidin-4-yl)-2-((benzyloxy)carbonyl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid as a white solid.

Workup

  1. customThe reaction flask was degassed
  2. additionrefilled with argon via balloon 3 times
  3. temperaturethe reaction mixture was refluxed for 4 h
  4. concentrationconcentrated in vacuo
  5. extractionextracted with EtOAc
  6. washThe combined organic layers were are washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by reverse phase silica gel column (H2O/NH4OH/MeOH)

Sources & evidence

ORD record
ord-70a8a0137a6f459e9cf7d28953c10fe9
Source dataset
uspto-grants-2015_12
Patent number
US09199994B2

Reaction notes

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