Lithium Hydroxide → HCID 86681234, compound

HRID 1848261Notes

Reaction equation

HRID 1848261 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](/[CH:28]=[CH:29]/[C:30]([O:32]CC)=[O:31])=[CH:27][C:22]=4[N:21]=[CH:20]3)[CH:15]=[CH:14][C:12]=2[N:13]=1.[Li+].[OH-]>C1COCC1>[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](/[CH:28]=[CH:29]/[C:30]([OH:32])=[O:31])=[CH:27][C:22]=4[N:21]=[CH:20]3)[CH:15]=[CH:14][C:12]=2[N:13]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 86681233HCID 86681233, compound

Product 1

HCID 86681234HCID 86681234, compoundYield 16%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (E)-ethyl 3-(1-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)-1H-benzo[d]imidazol-5-yl)acrylate from the previous step in THF (2 mL) was added 1M aq LiOH (2 mL) and the mixture was stirred at rt for 48 h. The mixture was then acidified and concentrated under reduced pressure. The residue was purified directly 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 Varian Pursuit XRs diphenyl column as the stationary phase to afford (E)-3-(1-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)-1H-benzo[d]imidazol-5-yl)acrylic acid as a solid (22 mg, 16%). 1H NMR (500 MHz, DMSO-d6) δ 8.46 (s, 1H), 7.90-8.01 (m, 2H), 7.68 (d, J=15.8 Hz, 1H), 7.66 (d, J=1.0 Hz, 1H), 7.58 (s, 2H), 7.29 (d, J=10 Hz, 1H), 7.20 (dd, J=1.2, 8.1 Hz, 1H), 6.48 (d, J=15.8 Hz, 1H), 5.48 (s, 2H), 4.73 (br s, 1H), 3.47-3.57 (br m, 2H), 2.02 (m, 1H), 1.86 (m, 1H), 1.55-1.67 (m, 2H), 1.12-1.32 (m, 4H). LCMS (ESI) m/z 449 (M+H)+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was purified directly 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 Varian Pursuit XRs diphenyl column as the stationary phase

Sources & evidence

ORD record
ord-5a7bc10748d24364a4b4b92dd6ee10ce
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

Loading…