Sodium hydride → 2-benzyl 3-ethyl 8-(4-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)-1,3,5-triazin-2-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate

HRID 1499210Notes

Reaction equation

HRID 1499210 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([OH:13])[C:9]([F:12])([F:11])[F:10])=[C:4]([N:14]2[CH:18]=[CH:17][C:16]([CH3:19])=[N:15]2)[CH:3]=1.[H-].[Na+].[NH2:22][C:23]1[N:28]=[C:27](Cl)[N:26]=[C:25]([N:30]2[CH2:54][CH2:53][C:33]3([CH2:37][N:36]([C:38]([O:40][CH2:41][C:42]4[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=4)=[O:39])[CH:35]([C:48]([O:50][CH2:51][CH3:52])=[O:49])[CH2:34]3)[CH2:32][CH2:31]2)[N:24]=1>C1COCC1>[NH2:22][C:23]1[N:28]=[C:27]([O:13][C@H:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=2[N:14]2[CH:18]=[CH:17][C:16]([CH3:19])=[N:15]2)[C:9]([F:12])([F:11])[F:10])[N:26]=[C:25]([N:30]2[CH2:54][CH2:53][C:33]3([CH2:37][N:36]([C:38]([O:40][CH2:41][C:42]4[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=4)=[O:39])[CH:35]([C:48]([O:50][CH2:51][CH3:52])=[O:49])[CH2:34]3)[CH2:32][CH2:31]2)[N:24]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 25210912(alphaR)-4-Chloro-2-(3-methyl-1H-pyrazol-1-yl)-alpha-(trifluoromethyl)benzenemethanolHCID 1179478002-Benzyl 3-ethyl 8-(4-amino-6-chloro-1,3,5-triazin-2-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate2×

Product 1

HCID 1179528232-benzyl 3-ethyl 8-(4-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)-1,3,5-triazin-2-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethanol (380 mg, 1.3 mmol) in 10 mL of THF was added NaH (60 mg, 1.4 mmol) and the reaction was stirred at RT for 30 min. After this time, 2-benzyl 3-ethyl 8-(4-amino-6-chloro-1,3,5-triazin-2-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate (product from Step 1, Example 39a) (570 mg, 1.2 mmol) was added and the reaction was heated to 50° C. for 12 h. After this time, the reaction was cooled to RT, quenched with methanol and concentrated in vacuo. Normal phase silica gel chromatography (EtOAc/heptane) provided 2-benzyl 3-ethyl 8-(4-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)-1,3,5-triazin-2-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate as a white solid.

Workup

  1. temperaturethe reaction was heated to 50° C. for 12 h
  2. temperatureAfter this time, the reaction was cooled to RT
  3. customquenched with methanol
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d40232ce55664435a3f55420e73dfb10
Source dataset
uspto-grants-2015_12
Patent number
US09199994B2

Reaction notes

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