Sodium Carbonate → (S)-2-tert-butyl 3-ethyl 8-(2-amino-6-((R)-1-(4-chloro-3'-(methylsulfonyl)-[1,1'-biphenyl]-2-yl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate

HRID 1499222Notes

Reaction equation

HRID 1499222 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:29][CH2:28][C:11]3([CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C@H:13]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:12]3)[CH2:10][CH2:9]2)[CH:5]=[C:4]([O:30][C@H:31]([C:36]2[CH:41]=[C:40]([Cl:42])[CH:39]=[CH:38][C:37]=2Br)[C:32]([F:35])([F:34])[F:33])[N:3]=1.[CH3:44][S:45]([C:48]1[CH:49]=[C:50](B(O)O)[CH:51]=[CH:52][CH:53]=1)(=[O:47])=[O:46].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:29][CH2:28][C:11]3([CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C@H:13]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:12]3)[CH2:10][CH2:9]2)[CH:5]=[C:4]([O:30][C@H:31]([C:36]2[CH:41]=[C:40]([Cl:42])[CH:39]=[CH:38][C:37]=2[C:52]2[CH:51]=[CH:50][CH:49]=[C:48]([S:45]([CH3:44])(=[O:47])=[O:46])[CH:53]=2)[C:32]([F:35])([F:34])[F:33])[N:3]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27735423-(Methylsulfonyl)phenylboronic acidHCID 117952220(S)-2-tert-butyl 3-ethyl 8-(2-amino-6-((R)-1-(2-bromo-5-chlorophenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate

Product 1

HCID 117952300(S)-2-tert-butyl 3-ethyl 8-(2-amino-6-((R)-1-(4-chloro-3'-(methylsulfonyl)-[1,1'-biphenyl]-2-yl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of (S)-2-tert-butyl 3-ethyl 8-(2-amino-6-((R)-1-(2-bromo-5-chlorophenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate (660 mg, 0.95 mmol) in dioxane (12 mL) was added (3-(methylsulfonyl)phenyl)boronic acid (285 mg, 1.43 mmol), Pd2(dppf)Cl2 (70 mg, 0.095 mmol) and Na2CO3 (6.0 mL, 2.0 M, aq). The reaction was heated to 90° C. for 2 h, then cooled to RT, concentrated in vacuo. The residue was taken up in CH2Cl2, washed with brine, and extracted with CH2Cl2. The combined organic layers were dried over Na2SO4. Purification by normal phase silica gel column (EtOAc/heptane) provided (S)-2-tert-butyl 3-ethyl 8-(2-amino-6-((R)-1-(4-chloro-3′-(methylsulfonyl)-[1,1′-biphenyl]-2-yl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate as a white solid.

Workup

  1. temperaturecooled to RT
  2. concentrationconcentrated in vacuo
  3. washwashed with brine
  4. extractionextracted with CH2Cl2
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. customPurification by normal phase silica gel column (EtOAc/heptane)

Sources & evidence

ORD record
ord-0cabfe353bb84ec8a62fe4c92d8601c0
Source dataset
uspto-grants-2015_12
Patent number
US09199994B2

Reaction notes

Loading…