Water → HCID 86681232, compound

HRID 1848259Notes

Reaction equation

HRID 1848259 reaction equation
CS([C:4]1[S:5][C:6]2[CH:12]=[C:11]([CH2:13][N:14]3[CH:19]=[CH:18][N:17]=[C:16]([N:20]4[CH2:25][CH2:24][O:23][CH2:22][CH2:21]4)[C:15]3=[O:26])[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.O>CC(N(C)C)=O>[OH:34][C@@H:29]1[CH2:30][CH2:31][CH2:32][CH2:33][C@H:28]1[NH:27][C:4]1[S:5][C:6]2[CH:12]=[C:11]([CH2:13][N:14]3[CH:19]=[CH:18][N:17]=[C:16]([N:20]4[CH2:25][CH2:24][O:23][CH2:22][CH2:21]4)[C:15]3=[O:26])[CH:10]=[CH:9][C:7]=2[N:8]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 735777(1R,2R)-2-AminocyclohexanolHCID 86681231HCID 86681231, compound

Product 1

HCID 86681232HCID 86681232, compoundYield 42.5%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 1-((2-(methylsulfinyl)benzo[d]thiazol-6-yl)methyl)-3-morpholino pyrazin-2(1H)-one (250 mg, 0.64 mmol), (1R,2R)-2-aminocyclohexanol (221 mg, 1.92 mmol) and DIEA (248 mg, 1.92 mmol) in DMA (6.6 mL) was stirred at 130° C. for 16 h. The reaction mixture was cooled to rt and poured into water (30 mL). The mixture extracted with ethyl acetate (3×100 mL) and the combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 1:5 petroleum ether/ethyl acetate to give 1-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)-3-morpholinopyrazin-2(1H)-one as a light yellow solid (120 mg, 26.5%). 1H NMR (300 MHz, DMSO-d6) δ 7.96 (d, J=7.2 Hz, 1H), 7.63 (s, 1H), 7.30 (d, J=8.4 Hz, 1H), 7.18-7.22 (m, 2H), 6.90 (d, J=4.8 Hz, 1H), 5.01 (s, 2H), 4.72 (d, J=5.1 Hz, 1H), 3.65 (s, 8H), 3.55-3.52 (m, 1H), 3.36-3.31 (m, 1H), 2.07-2.02 (m, 1H), 1.90-1.86 (m, 1H), 1.63-1.62 (m, 2H), 1.30-1.22 (m, 4H). LCMS (ESI) m/z 442 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. extractionThe mixture extracted with ethyl acetate (3×100 mL)
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with 1:5 petroleum ether/ethyl acetate

Sources & evidence

ORD record
ord-243e02ca5adc440cbb5110cff25bd70f
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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