Sodium Carbonate → (S)-2-benzyl 3-ethyl 8-(6-((R)-1-(4-bromo-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)-2-methylpyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate

HRID 1499182Notes

Reaction equation

HRID 1499182 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]([CH3:21])[N:15]=2)[C:9]([F:12])([F:11])[F:10])=[C:4]([N:22]2[CH:26]=[CH:25][C:24]([CH3:27])=[N:23]2)[CH:3]=1.[CH2:28]1[C:32]2([CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)[CH2:31][C@@H:30]([C:38]([O:40][CH2:41][CH3:42])=[O:39])[N:29]1[C:43]([O:45][CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)=[O:44].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([O:13][C:14]2[N:15]=[C:16]([CH3:21])[N:17]=[C:18]([N:35]3[CH2:34][CH2:33][C:32]4([CH2:28][N:29]([C:43]([O:45][CH2:46][C:47]5[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=5)=[O:44])[C@H:30]([C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:31]4)[CH2:37][CH2:36]3)[CH:19]=2)[C:9]([F:12])([F:11])[F:10])=[C:4]([N:22]2[CH:26]=[CH:25][C:24]([CH3:27])=[N:23]2)[CH:3]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 1179417652-Benzyl 3-ethyl (3S)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylateHCID 117942162(R)-4-(1-(4-bromo-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)-6-chloro-2-methylpyrimidine

Product 1

HCID 117952574(S)-2-benzyl 3-ethyl 8-(6-((R)-1-(4-bromo-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)-2-methylpyrimidin-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 (R)-4-(1-(4-bromo-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)-6-chloro-2-methylpyrimidine (21 g) in dioxane (200 ml) was added (S)-2-benzyl 3-ethyl 2,8-diazaspiro[4.5]decane-2,3-dicarboxylate (15 g) and Na2CO3 (14 g). The reaction was heated to 90° C. for 48 h, then cooled to RT, filtered, and concentrated in vacuo. Purification of the residue on normal phase column chromatography on silica gel (EtOAc/heptane) provided (S)-2-benzyl 3-ethyl 8-(6-((R)-1-(4-bromo-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)-2-methylpyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate as an off-white solid.

Workup

  1. temperaturecooled to RT
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo
  4. customPurification of the residue on normal phase column chromatography on silica gel (EtOAc/heptane)

Sources & evidence

ORD record
ord-5a26f6efb02d4295b38bf6221a8c4cb8
Source dataset
uspto-grants-2015_12
Patent number
US09199994B2

Reaction notes

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