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

HRID 1749487Notes

Reaction equation

HRID 1749487 reaction equation
[CH3:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2CCN)[N:5]=[N:4][N:3]=1.[OH:16][C@H:17]1[CH2:22][CH2:21][C@@H:20]([NH:23][C:24]2[C:29]([C:30]#[N:31])=[CH:28][N:27]=[C:26](S(C)(=O)=O)[N:25]=2)[CH2:19][C:18]1([CH3:37])[CH3:36].O[C@H]1CC[C@@H:42]([NH:45]C2C(C#N)=CN=C(S(C)=O)N=2)[CH2:41]C1(C)C.CCN(C(C)C)C(C)C>>[OH:16][C@H:17]1[CH2:22][CH2:21][C@@H:20]([NH:23][C:24]2[C:29]([C:30]#[N:31])=[CH:28][N:27]=[C:26]([NH:45][CH2:42][CH2:41][C:11]3[CH:10]=[CH:9][CH:8]=[C:7]([N:6]4[C:2]([CH3:1])=[N:3][N:4]=[N:5]4)[CH:12]=3)[N:25]=2)[CH2:19][C:18]1([CH3:37])[CH3:36]

Participants

5

Reactant 4

HCID 81531DiisopropylethylamineHCID 825065682-(2-(5-methyl-1H-tetrazol-1-yl)phenyl)ethanamineHCID 1181621034-(((1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl)amino)-2-(methylsulfonyl)pyrimidine-5-carbonitrileHCID 1181621344-(((1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl)amino)-2-(methylsulfinyl)pyrimidine-5-carbonitrile

Product 1

HCID 1181622534-((1R,4S)-4-Hydroxy-3,3-dimethylcyclohexylamino)-2-(3-(5-methyl-1H-tetrazol-1-yl)phenethylamino)pyrimidine-5-carbonitrileYield 21%

Conditions

Temperature
100 °C

Procedure

A mixture of 2-(2-(5-methyl-1H-tetrazol-1-yl)phenyl)ethanamine (85 mg, 0.42 mmol), 4-(((1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl)amino)-2-(methylsulfonyl)pyrimidine-5-carbonitrile and 4-(((1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl)amino)-2-(methylsulfinyl)pyrimidine-5-carbonitrile (90 mg, 0.27 mmol) and DIEA (105 mg, 0.81 mmol) was stirred at 100° C. under microwave irradiation for 1.5 h. After cooling to room temperature, the reaction mixture was concentrated and the residue was purified by standard methods to give the title compound (44.3 mg, 0.073 mmol, 21% yield). 1H NMR (400 MHz, CD3OD) δ (ppm) 7.92 (m, 1H), 7.50-7.40 (m, 2H), 7.34-7.25 (m, 2H), 4.25-4.15 (m, 1H), 3.68-3.49 (m, 2H), 3.25-3.22 (m, 1H), 3.00-2.87 (m, 2H), 2.46 (s, 3H), 1.79-1.22 (m, 6H), 0.88-0.83 (m, 6H). MS (ESI) m/z 448.2 [M+H]+.

Workup

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

Sources & evidence

ORD record
ord-51dfac5189ad41f8b97ac05190b80155
Source dataset
uspto-grants-2015_10
Patent number
US09156798B2

Reaction notes

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