Ammonium Hydroxide → 5-(2-Isopropyl-4,5-dimethoxybenzyl)-N4-ethylpyrimidine-2,4-diamine

HRID 38333Notes

Reaction equation

[CH2:1]([NH:3][C:4]1[C:9]([CH2:10][C:11]2[CH:16]=[C:15]([O:17][CH3:18])[C:14]([O:19][CH3:20])=[CH:13][C:12]=2[CH:21]([CH3:23])[CH3:22])=[CH:8][N:7]=[C:6](S(C)(=O)=O)[N:5]=1)[CH3:2].[NH4+:28].[OH-]>C(COC)OC>[CH2:1]([NH:3][C:4]1[C:9]([CH2:10][C:11]2[CH:16]=[C:15]([O:17][CH3:18])[C:14]([O:19][CH3:20])=[CH:13][C:12]=2[CH:21]([CH3:23])[CH3:22])=[CH:8][N:7]=[C:6]([NH2:28])[N:5]=1)[CH3:2]

Participants

Conditions

Temperature: 145 °C

Procedure

To ethyl-[5-(2-isopropyl-4,5-dimethoxy-benzyl)-2-methanesulfonyl-pyrimidin-4-yl]-amine (0.078 g, 0.2 mmol) in microwave reactor vial was added 2.0 mL dimethoxy ethane and 0.5 mL concentrated NH4OH. The vial was capped and placed in a microwave reactor. The internal temperature was warmed to 145° C. After 2 hours an additional portion of 0.4 mL concentrated NH4OH was added and the mixture was heated an additional 2 hours. The mixture was cooled and concentrated in vacuo. Purification via flash chromatography (96:4 CH2Cl2/MeOH) afforded N*4*-ethyl-5-(2-isopropyl-4,5-dimethoxy-benzyl)-pyrimidine-2,4-diamine (0.031 g, 47%) as a pale yellow solid; Mass Spec M+H=329. Use of different alkyllithium reagents in step 1 and/or different substituted amines in steps 6 and 8 of the above procedure afforded additional compounds under the same or very similar reaction conditions. Additional compounds made by the procedure of Example 3 are shown in Table 1.

Workup

customThe vial was capped
customplaced in a microwave reactor
temperaturethe mixture was heated an additional 2 hours
temperatureThe mixture was cooled
concentrationconcentrated in vacuo
customPurification via flash chromatography (96:4 CH2Cl2/MeOH)

Sources & evidence

ORD record: ord-da15c827368045208bb0de6c0c2a5074
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08524725B2

Reaction notes

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