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

HRID 1499191Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C@@H:9]([O:14][C:15]1[CH:20]=[C:19](Cl)[N:18]=[C:17]([NH2:22])[N:16]=1)[C:10]([F:13])([F:12])[F:11].[CH2:23]1[C:27]2([CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)[CH2:26][C@@H:25]([C:33]([O:35][CH2:36][CH3:37])=[O:34])[N:24]1[C:38]([O:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[O:39].C([O-])(O)=O.[Na+]>O1CCOCC1>[NH2:22][C:17]1[N:18]=[C:19]([N:30]2[CH2:29][CH2:28][C:27]3([CH2:23][N:24]([C:38]([O:40][CH2:41][C:42]4[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=4)=[O:39])[C@H:25]([C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH2:26]3)[CH2:32][CH2:31]2)[CH:20]=[C:15]([O:14][C@H:9]([C:3]2[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=2[Br:1])[C:10]([F:13])([F:12])[F:11])[N:16]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of (R)-4-(1-(2-bromo-4-chlorophenyl)-2,2,2-trifluoroethoxy)-6-chloropyrimidin-2-amine (100 mg, 0.24 mmol, Step 1) in dioxane (5 mL) was added (S)-2-benzyl 3-ethyl 2,8-diazaspiro[4.5]decane-2,3-dicarboxylate (100 mg, 0.29 mmol), and NaHCO3 (300 mg, 3.5 mmol). After 5 h, an additional amount of NaHCO3 (300 mg, 3.5 mmol) was added and the reaction mixture was heated to 90° C. for 36 h. The reaction was then cooled to RT and filtered. Purification by normal phase silica gel column (EtOAc/heptane) provided (S)-2-benzyl 3-ethyl 8-(2-amino-6-((R)-1-(2-bromo-4-chlorophenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate as a white solid.

Workup

temperatureThe reaction was then cooled to RT
filtrationfiltered
customPurification by normal phase silica gel column (EtOAc/heptane)

Sources & evidence

ORD record: ord-188c8707edbb42fa803f7c5a5fdf4db7
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09199994B2

Reaction notes

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