Hydrochloric Acid → HCID 86681235, compound

HRID 1848263Notes

Reaction equation

HRID 1848263 reaction equation
[OH:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9]1[S:10][C:11]2[CH:17]=[C:16]([CH2:18][N:19]3[C:23]4[CH:24]=[CH:25][C:26]([C:28]5[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][CH:29]=5)=[CH:27][C:22]=4[N:21]=[CH:20]3)[CH:15]=[CH:14][C:12]=2[N:13]=1.Cl>C(Cl)Cl.O1CCOCC1>[NH:31]1[CH2:30][CH:29]=[C:28]([C:26]2[CH:25]=[CH:24][C:23]3[N:19]([CH2:18][C:16]4[CH:15]=[CH:14][C:12]5[N:13]=[C:9]([NH:8][C@@H:3]6[CH2:4][CH2:5][CH2:6][CH2:7][C@H:2]6[OH:1])[S:10][C:11]=5[CH:17]=4)[CH:20]=[N:21][C:22]=3[CH:27]=2)[CH2:33][CH2:32]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 86681236HCID 86681236, compound

Product 1

HCID 86681235HCID 86681235, compoundYield 6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of tert-butyl 4-(1-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)-1H-benzo[d]imidazol-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (30 mg, 0.05 mmol) from the previous step in DCM (3 mL) at 0° C. was added 4M HCl in 1,4-dioxane (0.3 mL), and the mixture was stirred at 0° C. for 5 min. The mixture concentrated under reduced pressure and the residue was purified by reverse-phase preparative HPLC using a mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Phenomenex Luna C-18 column as the stationary phase to afford (1R,2R)-2-((6-((5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol as a solid (1.38 mg, 5%). 1H NMR (500 MHz, DMSO-d6) δ 8.36 (s, 1H), 8.00 (d, J=7.4 Hz, 1H), 7.62 (d, J=5.9 Hz, 2H), 7.47 (d, J=8.9 Hz, 1H), 7.31 (d, J=8.4 Hz, 1H), 7.28 (d, J=8.4 Hz, 1H), 7.18 (dd, J=1.2, 8.1 Hz, 1H), 6.14 (br s, 1H), 5.44 (s, 2H), 3.47-3.57 (br m, 2H), 2.94 (t, J=5.4 Hz, 2H), 2.40 (br s, 2H), 2.02 (d, J=11.8 Hz, 1H), 1.85-1.87 (m, 6H), 1.57-1.66 (m, 2H), 1.12-1.30 (m, 4H); LCMS (ESI) m/z 460 (M+H)+.

Workup

  1. concentrationThe mixture concentrated under reduced pressure
  2. customthe residue was purified by reverse-phase preparative HPLC
  3. additiona mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Phenomenex Luna C-18 column as the stationary phase

Sources & evidence

ORD record
ord-12d840f4b4fb49f9bb025a3518018b68
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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