Hydrochloric Acid → N2-hydroxy-7,7-dimethyl-N5-[(1S)-1-phenylethyl]-6,7-dihydrothieno[3,2-c]pyridine-2,5(4H)-dicarboxamide

HRID 468678Notes

Reaction equation

HRID 468678 reaction equation
[CH3:1][C:2]1([CH3:21])[CH2:7][NH:6][CH2:5][C:4]2[CH:8]=[C:9]([C:11]([NH:13][O:14]C3CCCCO3)=[O:12])[S:10][C:3]1=2.C(N(CC)CC)C.[C:29]1([C@@H:35]([N:37]=[C:38]=[O:39])[CH3:36])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.Cl.O1CCOCC1>ClCCCl.O1CCCC1>[OH:14][NH:13][C:11]([C:9]1[S:10][C:3]2[C:2]([CH3:1])([CH3:21])[CH2:7][N:6]([C:38]([NH:37][C@H:35]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH3:36])=[O:39])[CH2:5][C:4]=2[CH:8]=1)=[O:12]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 2724173(S)-(-)-1-Phenylethyl isocyanateHCID 581576817,7-dimethyl-N-(tetrahydro-2H-pyran-2-yloxy)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamide

Product 1

HCID 58157558N2-hydroxy-7,7-dimethyl-N5-[(1S)-1-phenylethyl]-6,7-dihydrothieno[3,2-c]pyridine-2,5(4H)-dicarboxamideYield 47.7%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 7,7-dimethyl-N-(tetrahydro-2H-pyran-2-yloxy)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamide (31 mg, 0.1 mmol) and triethylamine (41.8 μL, 0.3 mmol) in 1,2-dichloroethane (1 mL) was added (S)-1-phenylethyl isocyanate (22.1 mg, 0.15 mmol). The reaction was stirred at room temperature overnight. The solution was evaporated to dryness and the residue obtained was redissolved in tetrahydrofuran (1 mL). 4.0 M of hydrochloric acid in 1,4-dioxane (1 mL, 4 mmol) was added and the reaction solution was stirred at room temperature for 2 hours. The solution was evaporated to dryness, redissolved in DMSO (1 mL) and purified on an Agilent 1100 LC/MSD instrument to afford the title compound (17.8 mg, 46%). LCMS (FA) ES+ 374; 1H NMR (400 MHz, MeOD) δ 7.35-7.24 (m, 5H), 7.20-7.15 (m, 1H), 5.01-4.91 (m, 1H), 4.50 (d, J=4.0 Hz, 2H), 3.50 (d, J=4.6 Hz, 2H), 1.47 (d, J=7.1 Hz, 3H), 1.30 (s, 6H).

Workup

  1. customThe solution was evaporated to dryness
  2. customthe residue obtained
  3. stirringthe reaction solution was stirred at room temperature for 2 hours
  4. customThe solution was evaporated to dryness
  5. dissolutionredissolved in DMSO (1 mL)
  6. custompurified on an Agilent 1100 LC/MSD instrument

Sources & evidence

ORD record
ord-eb325b68e0034beb8ab7f8f5312f9a69
Source dataset
uspto-grants-2014_01
Patent number
US08624040B2

Reaction notes

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