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

HRID 1848213Notes

Reaction equation

HRID 1848213 reaction equation
CC1(C)[N:6]([C:7]2[S:8][C:9]3[CH:15]=[C:14]([CH2:16][N:17]4[C:21]5[CH:22]=[CH:23][C:24]([O:26][CH2:27][CH2:28][OH:29])=[CH:25][C:20]=5[N:19]=[CH:18]4)[CH:13]=[CH:12][C:10]=3[N:11]=2)[C@@H:5]2[CH2:30][CH2:31][CH2:32][CH2:33][C@H:4]2[O:3]1.C(N(CC)CC)C>C(Cl)Cl.Cl>[OH:29][CH2:28][CH2:27][O:26][C:24]1[CH:23]=[CH:22][C:21]2[N:17]([CH2:16][C:14]3[CH:13]=[CH:12][C:10]4[N:11]=[C:7]([NH:6][C@@H:5]5[CH2:30][CH2:31][CH2:32][CH2:33][C@H:4]5[OH:3])[S:8][C:9]=4[CH:15]=3)[CH:18]=[N:19][C:20]=2[CH:25]=1

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 866811882-((1-((2-((3aR,7aR)-2,2-dimethylhexahydrobenzo[d]oxazol-3(2H)-yl)benzo[d]thiazol-6-yl)methyl)-1H-benzo[d]imidazol-5-yl)oxy)ethanol

Product 1

HCID 86681189(1R,2R)-2-((6-((5-(2-hydroxyethoxy)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanolYield 47%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred mixture of 2-((1-((2-((3aR,7aR)-2,2-dimethylhexahydrobenzo[d]oxazol-3(2H)-yl)benzo[d]thiazol-6-yl)methyl)-1H-benzo[d]imidazol-5-yl)oxy)ethanol (70 mg, 0.15 mmol) from the previous step in DCM (5 mL) at 0° C. was added methanolic HCl (3 drops). The reaction mixture was stirred at 0° C. for 10 min. The mixture was adjusted to pH˜7 by the addition of triethylamine and concentrated under reduced pressure. The residue was purified directly by reverse-phase preparative HPLC to afford ((1R,2R)-2-((6-((5-(2-hydroxyethoxy)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (30 mg, 47%) as a light yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 8.30 (s, 1H), 7.95 (d, J=7.2 Hz, 1H), 7.62 (s, 1H), 7.40 (d, J=9.0 Hz, 1H), 7.29 (d, J=8.1 Hz, 1H), 7.16-7.18 (m, 2H), 6.84 (m, 1H), 5.41 (s, 2H), 4.83 (br s, 1H), 4.72 (d, J=4.5 Hz, 1H), 3.98 (t, J=9.6 Hz, 2H), 3.71 (d, J=4.5 Hz, 2H), 3.52 (m, 1H), 3.33 (br s, 1H), 2.03 (m, 1H), 1.87 (m, 1H), 1.61-1.63 (m, 2H), 1.22-1.28 (m, 4H); LCMS (ESI) m/z 439 (M+H)+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was purified directly by reverse-phase preparative HPLC

Sources & evidence

ORD record
ord-044e78332285411e91302cf1eefb69f1
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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