Sodium Bicarbonate → (S)-2-benzyl 3-ethyl 8-(2-amino-6-((R)-1-(4-bromophenyl)-2,2,2-trifluoroethoxy)-pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate

HRID 1499253Notes

Reaction equation

HRID 1499253 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([O:13][C:14]2[CH:19]=[C:18](Cl)[N:17]=[C:16]([NH2:21])[N:15]=2)[C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=1.[CH2:22]1[C:26]2([CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[CH2:25][C@@H:24]([C:32]([O:34][CH2:35][CH3:36])=[O:33])[N:23]1[C:37]([O:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:38].C(=O)(O)[O-].[Na+]>O1CCOCC1>[NH2:21][C:16]1[N:17]=[C:18]([N:29]2[CH2:28][CH2:27][C:26]3([CH2:22][N:23]([C:37]([O:39][CH2:40][C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=4)=[O:38])[C@H:24]([C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:25]3)[CH2:31][CH2:30]2)[CH:19]=[C:14]([O:13][C@H:8]([C:5]2[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=2)[C:9]([F:12])([F:11])[F:10])[N:15]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 1179417652-Benzyl 3-ethyl (3S)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylateHCID 117942299(R)-4-(1-(4-bromophenyl)-2,2,2-trifluoroethoxy)-6-chloropyrimidin-2-amine

Product 1

HCID 117952820(S)-2-benzyl 3-ethyl 8-(2-amino-6-((R)-1-(4-bromophenyl)-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
100 °C

Procedure

To a solution of (R)-4-(1-(4-bromophenyl)-2,2,2-trifluoroethoxy)-6-chloropyrimidin-2-amine (19 mg, 0.50 mmol) in dioxane (25 ml) was added (S)-2-benzyl 3-ethyl 2,8-diazaspiro[4.5]decane-2,3-dicarboxylate (175 mg, 0.50 mmol) and sodium bicarbonate (210 mg, 0.25 mmol), and the reaction mixture was heated to 100° C. for 48 h. Then the reaction mixture was cooled to RT, and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. Purification by normal phase silica gel column (EtOAc/heptane) provided (S)-2-benzyl 3-ethyl 8-(2-amino-6-((R)-1-(4-bromophenyl)-2,2,2-trifluoroethoxy)-pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate as white solid.

Workup

  1. temperatureThen the reaction mixture was cooled to RT
  2. extractionextracted with EtOAc
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by normal phase silica gel column (EtOAc/heptane)

Sources & evidence

ORD record
ord-ace39f229f724c8daaa8af78fa4a11dc
Source dataset
uspto-grants-2015_12
Patent number
US09199994B2

Reaction notes

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