Diisopropylethylamine → 4-((3R,4R)-3-hydroxy-4-methylcyclohexylamino)-2-(1-methylcyclopropylamino)pyrimidine-5-carbonitrile

HRID 2280784Notes

Reaction equation

HRID 2280784 reaction equation
[CH3:1][C:2]1([NH:5][C:6]2[N:11]=[C:10](S(C)(=O)=O)[C:9]([C:16]#[N:17])=[CH:8][N:7]=2)[CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.Cl.[NH2:28][C@H:29]1[CH2:34][C@@H:33]([OH:35])[C@H:32]([CH3:36])[CH2:31][CH2:30]1>>[OH:35][C@H:33]1[C@H:32]([CH3:36])[CH2:31][CH2:30][CH:29]([NH:28][C:10]2[C:9]([C:16]#[N:17])=[CH:8][N:7]=[C:6]([NH:5][C:2]3([CH3:1])[CH2:4][CH2:3]3)[N:11]=2)[CH2:34]1

Participants

4

Reactant 3

HCID 81531DiisopropylethylamineHCID 712376902-(1-Methylcyclopropylamino)-4-(methylsulfonyl)pyrimidine-5-carbonitrileHCID 86676342(1R,2R,5R)-5-amino-2-methylcyclohexanol hydrochloride

Product 1

HCID 709813154-((3R,4R)-3-hydroxy-4-methylcyclohexylamino)-2-(1-methylcyclopropylamino)pyrimidine-5-carbonitrileYield 30%

Conditions

Temperature
90 °C

Procedure

To the reaction mixture of 2-(1-methylcyclopropylamino)-4-(methylsulfonyl)pyrimidine-5-carbonitrile from the previous step was added DIEA (2.14 mL, 12.22 mmol) and (1R,2R,5R)-5-amino-2-methylcyclohexanol hydrochloride (0.371 g, 2.241 mmol; synthesis described herein). The reaction was stirred at 90° C. for 16 h. Upon completion of reaction, as indicated by LCMS and TLC, the reaction mixture was concentrated and purified by silica gel chromatography using a gradient of 0%-60% ethyl acetate in hexanes. The product fractions were combined and concentrated to afford 4-((3R,4R)-3-hydroxy-4-methylcyclohexylamino)-2-(1-methylcyclopropylamino)pyrimidine-5-carbonitrile (0.185 g, 30% yield) as a pale yellow solid. MS (ESI) m/z 302.1 [M+1]+

Workup

  1. customsynthesis
  2. customUpon completion of reaction
  3. concentrationthe reaction mixture was concentrated
  4. custompurified by silica gel chromatography
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-cebafac5d45e49dcb0e652dae0cdb2d4
Source dataset
uspto-grants-2015_09
Patent number
US09139534B2

Reaction notes

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