Diisopropylethylamine → 2-Chloro-4-{2-[5-cyano-4-(4-hydroxy-3,3-dimethyl-cyclohexylamino)-pyrimidin-2-ylamino]-ethyl}-benzenesulfonamide

HRID 1749499Notes

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)=O)[N:10]=2)[CH2:4][C:3]1([CH3:22])[CH3:21].O[C@H]1CC[C@@H](NC2C(C#N)=CN=C(S(C)=O)N=2)CC1(C)C.[NH2:44][CH2:45][CH2:46][C:47]1[CH:52]=[CH:51][C:50]([S:53]([NH2:56])(=[O:55])=[O:54])=[C:49]([Cl:57])[CH:48]=1.CCN(C(C)C)C(C)C>C1COCC1>[Cl:57][C:49]1[CH:48]=[C:47]([CH2:46][CH2:45][NH:44][C:11]2[N:10]=[C:9]([NH:8][CH:5]3[CH2:6][CH2:7][CH:2]([OH:1])[C:3]([CH3:21])([CH3:22])[CH2:4]3)[C:14]([C:15]#[N:16])=[CH:13][N:12]=2)[CH:52]=[CH:51][C:50]=1[S:53]([NH2:56])(=[O:55])=[O:54]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 4-(((1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl)amino)-2-(methylsulfonyl)pyrimidine-5-carbonitrile (90 mg, 0.28 mmol) and 4-(((1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl)amino)-2-(methylsulfinyl)pyrimidine-5-carbonitrile, 4-(2-amino-ethyl)-2-chloro-benzenesulfonamide (90 mg, 0.38 mmol) and DIEA (72 mg, 0.56 mmol) in THF (4 mL) was stirred at 100° C. in a microwave reactor for 1 h. After cooling to room temperature, the reaction mixture was concentrated and the residue was purified by standard methods to afford the title compound (28.6 mg, 0.060 mmol, 26% yield). 1H NMR (400 MHz, CD3OD) δ (ppm) 7.93 (s, 1H), 7.85 (d, J=8.0 Hz, 1H), 7.35 (s, 1H), 7.20 (d, J=8.0 Hz, 1H), 4.26-4.12 (m, 1H), 3.66-3.46 (m, 2H), 3.31-3.25 (m, 1H), 2.87 (t, J=6.8 Hz, 2H), 1.86-1.35 (m, 6H), 0.90 (s, 3H), 0.88 (s, 3H). MS (ESI) m/z 479.1 [M+H]+.

Workup

temperatureAfter cooling to room temperature
concentrationthe reaction mixture was concentrated
customthe residue was purified by standard methods

Sources & evidence

ORD record: ord-3c863f31567f4c7b88b871d2ccea7284
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09156798B2

Reaction notes

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