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

HRID 1848211Notes

Reaction equation

HRID 1848211 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][N:29]6[CH2:34][CH2:33][O:32][CH2:31][CH2:30]6)=[CH:25][C:20]=5[N:19]=[CH:18]4)[CH:13]=[CH:12][C:10]=3[N:11]=2)[C@@H:5]2[CH2:35][CH2:36][CH2:37][CH2:38][C@H:4]2[O:3]1.C(N(CC)CC)C>C(Cl)Cl.Cl>[O:32]1[CH2:31][CH2:30][N:29]([CH2:28][CH2:27][O:26][C:24]2[CH:23]=[CH:22][C:21]3[N:17]([CH2:16][C:14]4[CH:13]=[CH:12][C:10]5[N:11]=[C:7]([NH:6][C@@H:5]6[CH2:35][CH2:36][CH2:37][CH2:38][C@H:4]6[OH:3])[S:8][C:9]=5[CH:15]=4)[CH:18]=[N:19][C:20]=3[CH:25]=2)[CH2:34][CH2:33]1

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 86681185(3aR,7aR)-2,2-dimethyl-3-(6-((5-(2-morpholinoethoxy)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)octahydrobenzo[d]oxazole

Product 1

HCID 86681187(1R,2R)-2-((6-((5-(2-morpholinoethoxy)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanolYield 26.3%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred mixture of (3aR,7aR)-2,2-dimethyl-3-(6-((5-(2-morpholino ethoxy)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)octahydrobenzo[d]oxazole (85 mg, 0.15 mmol) from the previous step in DCM (10 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 addition of triethylamine and then concentrated under reduced pressure. The residue was purified directly by reverse-phase preparative HPLC to afford (1R,2R)-2-((6-((5-(2-morpholinoethoxy)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (20 mg, 25%) as a light yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 8.30 (s, 1H), 7.97 (m, 1H), 7.62 (s, 1H), 7.39 (d, J=8.4 Hz, 1H), 7.29 (d, J=8.1 Hz, 1H), 7.17 (d, J=6.9 Hz, 2H), 6.83 (m, 1H), 5.41 (s, 2H), 4.73 (d, J=5.4 Hz, 1H), 4.08 (t, J=11.7 Hz, 2H), 3.57 (t, J=9.1 Hz, 4H), 3.47-3.52 (m, 2H), 2.68 (t, J=11.7 Hz, 2H), 2.46 (t, J=9.3 Hz, 4H), 2.02 (m, 1H), 1.87 (m, 1H), 1.59-1.63 (br s, 2H), 1.16-1.28 (m, 4H). LCMS (ESI) m/z 508 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-8e465de581774d28bce9c6f32d2391e5
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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