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

HRID 1499270Notes

Reaction equation

[Br:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][CH2:7][C:8]2[CH:13]=[C:12](Cl)[N:11]=[C:10]([NH2:15])[N:9]=2)=[CH:4][CH:3]=1.[CH2:18]1[C:22]2([CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)[CH2:21][C@@H:20]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[N:19]1[C:33]([O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:34].C([O-])(O)=O.[Na+]>O1CCOCC1>[NH2:15][C:10]1[N:11]=[C:12]([N:25]2[CH2:24][CH2:23][C:22]3([CH2:18][N:19]([C:33]([O:35][CH2:36][C:37]4[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=4)=[O:34])[C@H:20]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:21]3)[CH2:27][CH2:26]2)[CH:13]=[C:8]([CH2:7][O:6][C:5]2[CH:16]=[CH:17][C:2]([Br:1])=[CH:3][CH:4]=2)[N:9]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 4-((4-Bromophenoxy)methyl)-6-chloropyrimidin-2-amine (454 mg, 1.4 mmol), (S)-2-benzyl 3-ethyl 2,8-diazaspiro[4.5]decane-2,3-dicarboxylate (500 mg, 1.44 mmol) and NaHCO3 (605 mg, 7 mmol) in dioxane (5 mL) was heated to 100° C. for 12 h. The reaction was cooled to RT, concentrated in vacuo, and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo. Purification on normal phase silica gel (EtOAc/petroleum ether) provided (S)-2-benzyl 3-ethyl 8-(2-amino-6-((4-bromophenoxy)methyl)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate as a white solid.

Workup

temperatureThe reaction was cooled to RT
concentrationconcentrated in vacuo
extractionextracted with EtOAc
washThe combined organic layers were washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customPurification on normal phase silica gel (EtOAc/petroleum ether)

Sources & evidence

ORD record: ord-b29fc1474d934fceb9e18789e9773a41
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09199994B2

Reaction notes

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