Hydrochloric Acid → HCID 58204467, compound

HRID 1498376Notes

Reaction equation

HRID 1498376 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][C@@H:11]([C:14]2[CH:35]=[CH:34][C:17]3[C:18]4[N:22]([CH2:23][CH2:24][O:25][C:16]=3[CH:15]=2)[CH:21]=[C:20]([C:26]2[N:27]([CH:31]([CH3:33])[CH3:32])[N:28]=[CH:29][N:30]=2)[N:19]=4)[C@H:10]([OH:36])[CH2:9]1)=O)(C)(C)C.Cl>C(Cl)Cl.CO.O1CCOCC1>[CH:31]([N:27]1[C:26]([C:20]2[N:19]=[C:18]3[C:17]4[CH:34]=[CH:35][C:14]([CH:11]5[CH2:12][CH2:13][NH:8][CH2:9][CH:10]5[OH:36])=[CH:15][C:16]=4[O:25][CH2:24][CH2:23][N:22]3[CH:21]=2)=[N:30][CH:29]=[N:28]1)([CH3:33])[CH3:32]

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 131729887HCID 131729887, compound

Product 1

HCID 58204467HCID 58204467, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of trans-racemic-3-hydroxy-4-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-piperidine-1-carboxylic acid tert-butyl ester (180 mg, 0.36 mmol) in DCM (1 mL) and methanol (0.6 mL) was added 4M HCl in dioxane (1.6 mL) slowly and the reaction mixture stirred at RT for 2.5 hr before being concentrated in vacuo. The resultant residue was triturated in diethyl ether to give 4-(2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)piperidin-3-ol which was resolved to give the (3R,4R) enantiomer 303 as a white solid (172 mg, quantitative). LCMS: RT=2.41 min, [M+H]+ 395. 1H NMR 400 MHz (DMSO-d6) δ: 9.30 (1H, br, s), 9.10 (1H, br, s), 8.36 (1 H, d, J=8.28 Hz), 8.10 (1H, br, s), 8.06 (1H, s), 7.04 (1 H, d, J=8.38 Hz), 6.91 (1 H, s), 5.87 (1H, m), 4.53 (4 H, d, J=8.12 Hz), 3.90 (1H, br, m), 3.25 (2H, m), 2.78 (1H, m), 2.52 (2H, m), 1.80 (2H, m), 1.50 (1 H, d, J=6.58 Hz)

Workup

  1. concentrationbefore being concentrated in vacuo
  2. customThe resultant residue was triturated in diethyl ether

Sources & evidence

ORD record
ord-e0afb66915e9478594c746ce0652f61c
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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