Triethylamine → HCID 73775237, compound

HRID 712088Notes

Reaction equation

HRID 712088 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.Cl[C:31]([O:33][CH2:34][CH3:35])=[O:32]>C(Cl)Cl>[OH:22][C@@H:20]([C:9]1[N:8]([C@H:4]2[CH2:5][CH2:6][CH2:7][N:2]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[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

5

Reactant 3

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 86717543HCID 86717543, compound

Product 1

HCID 73775237HCID 73775237, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of (1R)-1-{1-[(3S)-piperidin-3-yl]-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-2-yl}ethanol hydrochloride (15 mg, 0.044 mmol) and triethylamine (18.5 μL, 0.133 mmol) in methylene chloride (0.3 mL) was added ethyl chloroformate (5.1 μL, 0.0531 mmol). The resulting mixture was stirred until completion then the solvent evaporated. The crude residue was purified using RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give 5.6 mg (34%) of the desired product. LCMS calculated for C18H23N4O3S (M+H)+: m/z=375.1. Found: 375.0. 1H NMR (300 MHz, CDCl3) δ 9.08 (d, J=1.3 Hz, 1H), 7.69 (dd, J=5.5 and 1.3 Hz, 1H), 7.62 (d, J=5.5 Hz, 1H), 5.21 (d, J=6.7 Hz, 1H), 4.83-4.68 (m, 1H), 4.43-4.23 (m, 2H), 4.15 (q, J=6.9 Hz, 2H), 3.93-3.66 (m, 1H), 3.18-3.01 (m, 1H), 2.76-2.60 (m, 1H), 2.20-2.10 (m, 1H), 2.00 (d, J=13.8 Hz, 1H), 1.79 (d, J=6.4 Hz, 3H), 1.70-1.61 (m, 2H), 1.30-1.16 (m, 3H) ppm.

Workup

  1. customthe solvent evaporated
  2. customThe crude residue was purified
  3. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min)

Sources & evidence

ORD record
ord-b149d5b15fc6481ca360b73ab55f6a06
Source dataset
uspto-grants-2015_11
Patent number
US09181271B2

Reaction notes

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