Diisopropylethylamine → 4-(((1S,4R)-4-Hydroxy-3,3-dimethylcyclohexyl)amino)-2-((2-(5-methyl-1H-tetrazol-1-yl)benzyl)amino)pyrimidine-5-carbonitrile

HRID 1749399Notes

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].O[C@@H]1CC[C@H](NC2C(C#N)=CN=C(S(C)(=O)=O)N=2)CC1(C)C.Cl.[CH3:45][C:46]1[N:50]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=2[CH2:57][NH2:58])[N:49]=[N:48][N:47]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[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]([NH:58][CH2:57][C:52]3[CH:53]=[CH:54][CH:55]=[CH:56][C:51]=3[N:50]3[C:46]([CH3:45])=[N:47][N:48]=[N:49]3)[N:10]=2)[CH2:4][C:3]1([CH3:21])[CH3:20]

Participants

Conditions

Temperature: 120 °C

Procedure

To a mixture of 4-(((1S,4R)-4-hydroxy-3,3-dimethylcyclohexyl)amino)-2-(methylsulfinyl)pyrimidine-5-carbonitrile and 4-(((1S,4R)-4-hydroxy-3,3-dimethylcyclohexyl)amino)-2-(methylsulfonyl)pyrimidine-5-carbonitrile (1.0 equiv) in dioxane (0.4M) was added (2-(5-methyl-1H-tetrazol-1-yl)phenyl)methanamine hydrochloride (1.0 equiv.) and DIEA (2.0 equiv.). The mixture was stirred at 120° C. in microwave for 2 h. After completion of the reaction and standard work-up, the desired product was obtained (37% yield). 1H-NMR (400 MHz, DMSO-d6) δ (ppm) 8.12 (s, 1H), 7.82-7.78 (m, 1H), 7.63-7.61 (m, 1H), 7.58-7.51 (m, 3H), 7.02-6.92 (m, 1H), 4.32-4.17 (m, 3H), 4.01-3.99 (m, 1H), 3.21-3.14 (m, 1H), 2.41-2.36 (m, 3H), 1.65-1.47 (m, 1H), 1.36 (br, 1H), 1.23-1.17 (m, 2H), 0.81 (s, 3H), 0.73 (s, 3H); MS (ESI) m/z 434.2 [M+H]+.

Workup

customAfter completion of the reaction and standard work-up

Sources & evidence

ORD record: ord-02f02d548ef24261916b0f4d5a3211ee
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09156798B2

Reaction notes

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