Isopropylamine → 4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-2-(isopropylamino)pyrimidine-5-carbonitrile

HRID 2280751Notes

Reaction equation

HRID 2280751 reaction equation
[OH:1][C@H:2]1[C@H:7]([CH3:8])[CH2:6][CH2:5][C@@H:4]([NH:9][C:10]2[C:15]([C:16]#[N:17])=[CH:14][N:13]=[C:12](S(C)(=O)=O)[N:11]=2)[CH2:3]1.[CH3:22][CH:23]([NH2:25])[CH3:24].CCN(C(C)C)C(C)C>>[OH:1][C@H:2]1[C@H:7]([CH3:8])[CH2:6][CH2:5][C@@H:4]([NH:9][C:10]2[C:15]([C:16]#[N:17])=[CH:14][N:13]=[C:12]([NH:25][CH:23]([CH3:24])[CH3:22])[N:11]=2)[CH2:3]1

Participants

4

Reactant 3

HCID 6363IsopropylamineHCID 81531DiisopropylethylamineHCID 712371744-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-2-(methylsulfonyl)pyrimidine-5-carbonitrile

Product 1

HCID 712373964-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-2-(isopropylamino)pyrimidine-5-carbonitrileYield 92%

Conditions

Temperature
80 °C

Procedure

To the solution of 4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-2-(methylsulfonyl)pyrimidine-5-carbonitrile (446 mg, 1.437 mmol) from the previous step was added propan-2-amine (0.367 mL, 4.31 mmol) and DIEA (1.004 mL, 5.75 mmol). The reaction was stirred at 80° C. for 4 h and then allowed to cool to ambient temperature. The solvent was evaporated under reduced pressure and the residue was purified by silica gel chromatography (0-90% ethyl acetate in hexanes) to afford 4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-2-(isopropylamino)pyrimidine-5-carbonitrile (381 mg, 1.317 mmol, 92% yield). MS (ESI) m/z 290.2 [M+1]+

Workup

  1. temperatureto cool to ambient temperature
  2. customThe solvent was evaporated under reduced pressure
  3. customthe residue was purified by silica gel chromatography (0-90% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-eab4e1e9b2b8410a8e054ed2d7816e60
Source dataset
uspto-grants-2015_09
Patent number
US09139534B2

Reaction notes

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