Diisopropylethylamine → (1R,2R)-2-((6-((5-(benzyloxy)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol

HRID 1848163Notes

Reaction equation

HRID 1848163 reaction equation
[CH2:1]([O:8][C:9]1[CH:30]=[CH:29][C:12]2[N:13]([CH2:16][C:17]3[CH:28]=[CH:27][C:20]4[N:21]=[C:22](S(C)=O)[S:23][C:19]=4[CH:18]=3)[CH:14]=[N:15][C:11]=2[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH2:32][C@@H:33]1[CH2:38][CH2:37][CH2:36][CH2:35][C@H:34]1[OH:39].CCN(C(C)C)C(C)C>CC(N(C)C)=O>[CH2:1]([O:8][C:9]1[CH:30]=[CH:29][C:12]2[N:13]([CH2:16][C:17]3[CH:28]=[CH:27][C:20]4[N:21]=[C:22]([NH:32][C@@H:33]5[CH2:38][CH2:37][CH2:36][CH2:35][C@H:34]5[OH:39])[S:23][C:19]=4[CH:18]=3)[CH:14]=[N:15][C:11]=2[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 12228412Cyclohexanol, 2-amino-, hydrochloride (1:1), (1R,2R)-HCID 866811316-((5-(benzyloxy)-1H-benzo[d]imidazol-1-yl)methyl)-2-(methylsulfinyl)benzo[d]thiazole

Product 1

HCID 86681132(1R,2R)-2-((6-((5-(benzyloxy)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanolYield 59.5%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
138 °C

Procedure

A stirred mixture of 6-((5-(benzyloxy)-1H-benzo[d]imidazol-1-yl)methyl)-2-(methylsulfinyl)benzo[d]thiazole (1.48 g, 3.4 mmol) from the previous step, (1R,2R)-2-aminocyclohexanol hydrochloride (1.29 g, 8.5 mmol), and DIEA (2.19 g, 17 mmol) in DMA (44 mL) was heated at 138° C. for 15 h. The reaction mixture was cooled to rt and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography eluting with 2 to 6% MeOH in DCM to afford (1R,2R)-2-((6-((5-(benzyloxy)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (0.98 g, 59%) as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 7.88 (s, 1H), 7.43-7.46 (m, 3H), 7.29-7.39 (m, 4H), 7.25 (s, 1H), 7.13-7.16 (m, 2H), 6.96 (m, 1H), 5.75 (br s, 1H), 5.31 (s, 2H), 5.09 (s, 2H), 3.46-3.56 (m, 2H), 2.07-2.18 (m, 2H), 1.71-1.77 (m, 2H), 1.26-1.40 (m, 4H); LCMS (ESI) m/z 485 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was purified by silica gel flash chromatography
  4. washeluting with 2 to 6% MeOH in DCM

Sources & evidence

ORD record
ord-0b8031d32e2b41228eeead0ff30cf448
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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