Methyl 3,9-diazaspiro[5.5]undecane-10-carboxylate → methyl 9-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-3,9-diazaspiro[5.5]undecane-2-carboxylate

HRID 1499267Notes

Reaction equation

[CH2:1]1[C:6]2([CH2:11][CH:10]([C:12]([O:14][CH3:15])=[O:13])[NH:9][CH2:8][CH2:7]2)[CH2:5][CH2:4][NH:3][CH2:2]1.Cl[C:17]1[CH:22]=[C:21]([O:23][C@H:24]([C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:30]=2[N:36]2[CH:40]=[CH:39][C:38]([CH3:41])=[N:37]2)[C:25]([F:28])([F:27])[F:26])[N:20]=[C:19]([NH2:42])[N:18]=1>O1CCOCC1>[NH2:42][C:19]1[N:18]=[C:17]([N:3]2[CH2:4][CH2:5][C:6]3([CH2:11][CH:10]([C:12]([O:14][CH3:15])=[O:13])[NH:9][CH2:8][CH2:7]3)[CH2:1][CH2:2]2)[CH:22]=[C:21]([O:23][C@H:24]([C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:30]=2[N:36]2[CH:40]=[CH:39][C:38]([CH3:41])=[N:37]2)[C:25]([F:27])([F:26])[F:28])[N:20]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of methyl 3,9-diazaspiro[5.5]undecane-10-carboxylate (30 mg, 0.14 mmol) in dioxane (2 mL)/1-PrOH (2 mL) was added 4-chloro-6-[(1R)-1-[4-chloro-2-(3-methylpyrazol-1-yl)phenyl]-2,2,2-trifluoro-ethoxy]pyrimidin-2-amine (92 mg, 0.22 mmol), and the reaction was heated at 100° C. under microwave for 3 h. The reaction was cooled to RT, and concentrated in vacuo. The residue was purified by reversed phase HPLC (MeOH/H2O/0.5% TFA) to provide methyl 9-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-3,9-diazaspiro[5.5]undecane-2-carboxylate as an off-white solid.

Workup

temperatureThe reaction was cooled to RT
concentrationconcentrated in vacuo
customThe residue was purified by reversed phase HPLC (MeOH/H2O/0.5% TFA)

Sources & evidence

ORD record: ord-391359f87c2346dba7a1a44763d53a41
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09199994B2

Reaction notes

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