Cesium carbonate → HCID 71548894, compound

HRID 1848076Notes

Reaction equation

HRID 1848076 reaction equation
[N:1]1[NH:2][N:3]=[N:4][C:5]=1[C:6]1[CH:7]=[C:8]2[N:14]=[CH:13][N:12]([CH2:15][C:16]3[CH:32]=[CH:31][C:19]4[N:20]=[C:21]([NH:23][C@@H:24]5[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]5[OH:30])[S:22][C:18]=4[CH:17]=3)[C:9]2=[N:10][CH:11]=1.[C:33]([O-])([O-])=O.[Cs+].[Cs+]>CI>[CH3:33][N:3]1[N:2]=[N:1][C:5]([C:6]2[CH:7]=[C:8]3[N:14]=[CH:13][N:12]([CH2:15][C:16]4[CH:32]=[CH:31][C:19]5[N:20]=[C:21]([NH:23][C@@H:24]6[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]6[OH:30])[S:22][C:18]=5[CH:17]=4)[C:9]3=[N:10][CH:11]=2)=[N:4]1

Participants

4

Reactant 2

HCID 10796Cesium carbonateHCID 71548743HCID 71548743, compound

Product 1

HCID 71548894HCID 71548894, compound

Reagents, catalysts & solvents 1

HCID 6328Methyl iodideSolvent

Conditions

Temperature
90 °C

Procedure

To the remaining portion of the reaction mixture from Example 93 were added excess Cs2CO3 (300 mg) and excess MeI (200 μL). The resulting mixture was heated at 90° C. for 4 h. LCMS showed that the reaction was mostly completed. After cooling to rt, the mixture was purified by preparative HPLC using a mixture of water (5% CH3CN, 0.05% AcOH) and CH3CN (0.05% AcOH) as the mobile phase and Varian Pursuit XRs Diphenyl column as the stationary phase to afford (1R,2R)-2-((6-((6-(2-methyl-2H-tetrazol-5-yl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (8 mg) as a white powder. The regiochemistry assignment of the compound was consistent with the result from a NMR Nuclear Overhauser Effect (NOE) experiment. 1H NMR (300 MHz, MeOH-d4) δ 9.17 (s, 1H), 8.69 (s, 1H), 8.55 (s, 1H), 7.67 (s, 1H), 7.25-7.41 (m, 2H), 5.58 (s, 2H), 4.36-4.51 (m, 3H), 3.57 (d, J=9.6 Hz, 1H), 3.36-3.49 (m, 1H), 2.13 (d, J=11.3 Hz, 1H), 2.01 (br s, 1H), 1.71 (d, J=10.0 Hz, 2H), 1.12-1.48 (m, 4H). LCMS (ESI) m/z 462 (M+H)+.

Workup

  1. temperatureAfter cooling to rt
  2. customthe mixture was purified by preparative HPLC
  3. additiona mixture of water (5% CH3CN, 0.05% AcOH) and CH3CN (0.05% AcOH) as the mobile phase and Varian Pursuit XRs Diphenyl column as the stationary phase

Sources & evidence

ORD record
ord-0efea6cd63914605bde43f8504cc162f
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

Loading…