Hydrochloric Acid → HCID 86717545, compound

HRID 712090Notes

Reaction equation

HRID 712090 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][CH2:5][C@H:4]([N:8]2[C:12]3=[C:13]4[S:19][CH:18]=[CH:17][C:14]4=[N:15][CH:16]=[C:11]3[N:10]=[C:9]2[C@H:20]([OH:22])[CH3:21])[CH2:3]1.C(N(CC)CC)C.[C:30]([CH2:34][CH2:35][C:36](Cl)=[O:37])([O:32]C)=[O:31].O.[OH-].[Li+].Cl>C(Cl)Cl.O>[OH:22][C@@H:20]([C:9]1[N:8]([C@H:4]2[CH2:5][CH2:6][CH2:7][N:2]([C:36](=[O:37])[CH2:35][CH2:34][C:30]([OH:32])=[O:31])[CH2:3]2)[C:12]2=[C:13]3[S:19][CH:18]=[CH:17][C:14]3=[N:15][CH:16]=[C:11]2[N:10]=1)[CH3:21]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 73888Butanoic acid, 4-chloro-4-oxo-, methyl esterHCID 168937Lithium hydroxide, monohydrateHCID 86717543HCID 86717543, compound

Product 1

HCID 86717545HCID 86717545, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (1R)-1-{1-[(3S)-piperidin-3-yl]-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-2-yl}ethanol hydrochloride (30.0 mg, 0.0885 mmol) (Example 50, step 4) and triethylamine (37.0 μL, 0.266 mmol) in methylene chloride (0. 5 mL) was added 3-(carbomethoxy)propionyl chloride (12.0 μL, 0.0974 mmol). The resulting mixture was stirred at room temperature for 2 h. Water and dichloromethane were added and the layers separated. The organic was concentrated. The crude residue was taken up in methanol (0.5 mL), tetrahydrofuran (50 μL), and water (40 μL). Lithium hydroxide, monohydrate (18 mg, 0.44 mmol) was added and the mixture stirred at room temperature for 3 h. The mixture was made slightly acidic by adding 1N HCl then concentrated. The mixture was dissolved in dichloromethane, stirred, filtered and concentrated to give 37 mg of clean, crude acid. LCMS calculated for C19H23N4O4S (M+H)+: m/z=403.1. Found: 403.2.

Workup

  1. customthe layers separated
  2. concentrationThe organic was concentrated
  3. stirringthe mixture stirred at room temperature for 3 h
  4. concentrationthen concentrated
  5. dissolutionThe mixture was dissolved in dichloromethane
  6. stirringstirred
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give 37 mg of clean, crude acid

Sources & evidence

ORD record
ord-06580b16326a42779e9cb5e46ae01aa0
Source dataset
uspto-grants-2015_11
Patent number
US09181271B2

Reaction notes

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