N-methyl-2-pyrrolidone → HCID 86681106, compound

HRID 1848136Notes

Reaction equation

HRID 1848136 reaction equation
[CH3:1][C:2]1[CH:23]=[CH:22][C:5]2[N:6]([CH2:9][C:10]3[CH:21]=[CH:20][C:13]4[N:14]=[C:15](S(C)=O)[S:16][C:12]=4[CH:11]=3)[CH:7]=[N:8][C:4]=2[CH:3]=1.[NH2:24][C@@H:25]1[CH2:30][CH2:29][CH2:28][CH2:27][C@H:26]1[OH:31].CCN(C(C)C)C(C)C.CN1C(=O)CCC1>CCOC(C)=O>[CH3:1][C:2]1[CH:23]=[CH:22][C:5]2[N:6]([CH2:9][C:10]3[CH:21]=[CH:20][C:13]4[N:14]=[C:15]([NH:24][C@@H:25]5[CH2:30][CH2:29][CH2:28][CH2:27][C@H:26]5[OH:31])[S:16][C:12]=4[CH:11]=3)[CH:7]=[N:8][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 735777(1R,2R)-2-AminocyclohexanolHCID 86681105HCID 86681105, compound

Product 1

HCID 86681106HCID 86681106, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

A stirred mixture of 6-((5-methyl-1H-benzo[d]imidazol-1-yl)methyl)-2-(methylsulfinyl)benzo[d]thiazole (0.26 g, 0.76 mmol) from the previous step, (1R,2R)-2-aminocyclohexanol (0.26 g, 2.2 mmol), DIEA (0.98 g, 7.6 mmol) and NMP (2 mL) was heated at 130° C. for 12 h. The reaction mixture was cooled to rt, diluted with EtOAc (30 mL), and washed with water (10 mL×2). The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography eluting with 3% MeOH in DCM to afford (1R,2R)-2-((6-((5-methyl-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (79 mg, 89%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.30 (s, 1H), 7.91 (d, J=7.5 Hz, 1H), 7.61 (d, J=2.0 Hz, 1H), 7.39-7.42 (m, 2H), 7.28 (d, J=8.1 Hz, 1H), 7.16 (dd, J=8.4, 1.8 Hz, 1H), 7.02 (d, J=7.2 Hz, 1H), 5.42 (s, 2H), 4.69 (d, J=5.1 Hz, 1H), 3.39 (m, 1H), 3.33 (m, 1H), 2.38 (s, 3H), 2.03 (m, 1H), 1.86 (m, 1H), 1.59-1.63 (m, 2H), 1.21-1.23 (m, 4H); LCMS (ESI) m/z 393 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. washwashed with water (10 mL×2)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel flash chromatography
  7. washeluting with 3% MeOH in DCM

Sources & evidence

ORD record
ord-4a8c2d6a84154944b54c1d1086bf97f0
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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