Diisopropylethylamine → HCID 86681251, compound

HRID 1848276Notes

Reaction equation

HRID 1848276 reaction equation
[CH3:1][N:2]1[N:6]=[N:5][C:4]([C:7]2[CH:28]=[CH:27][C:10]3[N:11]([CH2:14][C:15]4[CH:26]=[CH:25][C:18]5[N:19]=[C:20](S(C)=O)[S:21][C:17]=5[CH:16]=4)[CH:12]=[N:13][C:9]=3[CH:8]=2)=[N:3]1.Cl.[NH2:30][C@@H:31]1[CH2:36][CH2:35][CH2:34][C@@H:33]([OH:37])[C@H:32]1[OH:38].CCN(C(C)C)C(C)C>CN1C(=O)CCC1>[CH3:1][N:2]1[N:6]=[N:5][C:4]([C:7]2[CH:28]=[CH:27][C:10]3[N:11]([CH2:14][C:15]4[CH:26]=[CH:25][C:18]5[N:19]=[C:20]([NH:30][C@@H:31]6[CH2:36][CH2:35][CH2:34][C@@H:33]([OH:37])[C@H:32]6[OH:38])[S:21][C:17]=5[CH:16]=4)[CH:12]=[N:13][C:9]=3[CH:8]=2)=[N:3]1

Participants

5

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 701504101161437-13-32×HCID 86681252HCID 86681252, compound

Product 1

HCID 86681251HCID 86681251, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

To a suspension of 6-((5-(2-methyl-2H-tetrazol-5-yl)-1H-benzo[d]imidazol-1-yl)methyl)-2-(methylsulfinyl)benzo[d]thiazole (330 mg, 0.8 mmol) and (1R,2S,3R)-3-aminocyclohexane-1,2-diol hydrochloride (391 mg, 2.4 mmol), prepared as described in Gauthier Errasti, et al, Org. Lett. 2009, 13, 2912-2915, in anhydrous NMP (3.0 mL) was added DIEA (703 μL, 4.0 mmol). The mixture was heated in a sealed tube at 120° C. for 15 h. Additional (1R,2S,3R)-3-aminocyclohexane-1,2-diol hydrochloride (258 mg, 1.6 mmol) and DIEA (703 μL, 4.0 mmol) were added, and the mixture was heated at 140° C. for a further 15 h. The mixture was cooled to rt and was purified by reverse-phase preparative HPLC using a mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase to afford (1R,2S,3R)-3-((6-((5-(2-methyl-2H-tetrazol-5-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexane-1,2-diol (37 mg, 10%) as a white powder. 1H NMR (500 MHz, DMSO-d6) δ 8.53 (s, 1H), 8.29 (s, 1H), 7.90-7.98 (m, 2H), 7.74 (d, J=8.4 Hz, 1H), 7.69 (s, 1H), 7.31 (m, 1H), 7.23 (dd, J=1.5, 8.4 Hz, 1H), 5.52 (s, 2H), 4.41 (s, 3H), 3.93 (m, 1H), 3.79 (m, 1H), 3.25 (m, 1H), 1.91 (m, 1H), 1.52-1.69 (m, 3H), 1.32-1.44 (m, 2H), 1.15-1.25 (m, 2H); LCMS (ESI) m/z 477 (M+H)+.

Workup

  1. customprepared
  2. temperaturethe mixture was heated at 140° C. for a further 15 h
  3. temperatureThe mixture was cooled to rt
  4. customwas purified by reverse-phase preparative HPLC
  5. additiona mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase

Sources & evidence

ORD record
ord-c53d1aac44704d83aebfa0bc2e5b4a1b
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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