4-(((1S,4R)-4-hydroxy-3,3-dimethylcyclohexyl)amino)-2-(methylsulfinyl)pyrimidine-5-carbonitrile → Cc-90005

HRID 1749394Notes

Reaction equation

HRID 1749394 reaction equation
[OH:1][C@@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]2[C:14]([C:15]#[N:16])=[CH:13][N:12]=[C:11](S(C)=O)[N:10]=2)[CH2:4][C:3]1([CH3:21])[CH3:20].[F:22][C:23]([F:35])([CH3:34])[CH2:24][O:25][C:26]1[C:31]([CH2:32][NH2:33])=[CH:30][N:29]=[CH:28][N:27]=1>O1CCOCC1>[F:35][C:23]([F:22])([CH3:34])[CH2:24][O:25][C:26]1[C:31]([CH2:32][NH:33][C:11]2[N:10]=[C:9]([NH:8][C@@H:5]3[CH2:6][CH2:7][C@H:2]([OH:1])[C:3]([CH3:21])([CH3:20])[CH2:4]3)[C:14]([C:15]#[N:16])=[CH:13][N:12]=2)=[CH:30][N:29]=[CH:28][N:27]=1

Participants

4

Reactant 2

HCID 1181621144-(((1S,4R)-4-hydroxy-3,3-dimethylcyclohexyl)amino)-2-(methylsulfinyl)pyrimidine-5-carbonitrileHCID 118162151C-[4-(2,2-Difluoro-propoxy)-pyrimidin-5-yl]-methylamine

Product 1

HCID 118162109Cc-90005Yield 69.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 4-(((1S,4R)-4-hydroxy-3,3-dimethylcyclohexyl)amino)-2-(methylsulfinyl)pyrimidine-5-carbonitrile (1.0 equiv) and (4-(2,2-difluoropropoxyl)pyrimidin-5-yl)methanamine (1.5 equiv) in dioxane (0.15 M) was heated at 110° C. for 1 h. Standard work-up provided 2-(((4-(2,2-difluoropropoxyl)pyrimidin-5-yl)methyl)amino)-4-(((1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl)amino)pyrimidine-5-carbonitrile (69.6% yield). 1H NMR (400 MHz, DMSO-d6): δ (ppm) 8.72 (s, 1H), 8.26 (s, 1H), 8.18 (s, 1H), 7.99 (t, J=5.66 Hz, 1H), 7.17 (d, J=7.81 Hz, 1H), 4.64 (t, J=12.89 Hz, 2H), 4.39-4.49 (m, 2H), 4.29 (d, J=3.51 Hz, 1H), 3.85-4.00 (m, 1H), 3.12 (br. s., 1H), 1.73 (t, J=19.14 Hz, 4H), 1.42-1.55 (m, 3H), 1.21-1.33 (m, 3H), 1.10 (br. s., 1H), 0.59-0.78 (m, 5H). MS (ESI) m/z 448.2 [M+1]+.

Sources & evidence

ORD record
ord-b85067b9ed9d490aa5a86520714890c4
Source dataset
uspto-grants-2015_10
Patent number
US09156798B2

Reaction notes

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