Diisopropylethylamine → HCID 86681222, compound

HRID 1848249Notes

Reaction equation

HRID 1848249 reaction equation
CS([C:4]1[S:5][C:6]2[CH:12]=[C:11]([CH2:13][N:14]3[C:18]4=[N:19][CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:22]=[C:17]4[N:16]=[CH:15]3)[CH:10]=[CH:9][C:7]=2[N:8]=1)=O.[NH2:27][C@@H:28]1[CH2:33][CH2:32][CH2:31][CH2:30][C@H:29]1[OH:34].CCN(C(C)C)C(C)C>CC(N(C)C)=O.CCOC(C)=O>[F:25][C:23]([F:24])([F:26])[C:21]1[CH:22]=[C:17]2[N:16]=[CH:15][N:14]([CH2:13][C:11]3[CH:10]=[CH:9][C:7]4[N:8]=[C:4]([NH:27][C@@H:28]5[CH2:33][CH2:32][CH2:31][CH2:30][C@H:29]5[OH:34])[S:5][C:6]=4[CH:12]=3)[C:18]2=[N:19][CH:20]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 735777(1R,2R)-2-AminocyclohexanolHCID 86681221HCID 86681221, compound

Product 1

HCID 86681222HCID 86681222, compoundYield 31.8%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 2-(methylsulfinyl)-6-((6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazole (180 mg, 0.45 mmol), (1R,2R)-2-aminocyclohexanol (112 mg, 0.97 mmol) and DIEA (261 mg, 2 mmol) in DMA (2 mL) was stirred at 130° C. overnight. The reaction mixture was diluted with EtOAc and washed with brine. The organic layer was dried over NaSO4, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC to afford (1R,2R)-2-((6-((6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol as a yellow solid (64 mg, 31.8%). 1H NMR (300 MHz, DMSO-d6) δ 8.84 (s, 1H), 8.78 (d, J=1.2 Hz, 1H), 8.55 (d, J=1.5 Hz, 1H), 7.95 (d, J=7.8 Hz, 1H), 7.68 (d, J=1.5 Hz, 1H), 7.29 (d, J=7.8 Hz, 1H), 7.25-7.22 (m, 1H), 5.55 (s, 2H), 4.71 (d, J=5.1 Hz, 1H), 3.52-3.50 (m, 1H), 3.37-3.33 (m, 1H), 2.08-2.01 (m, 1H), 1.87-1.85 (m, 1H), 1.64-1.60 (m, 2H), 1.29-1.19 (m, 4H). LCMS (ESI) m/z 448 (M+H)+.

Workup

  1. washwashed with brine
  2. dry with materialThe organic layer was dried over NaSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-020047345bf64d79b6a30590ac7837bd
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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