Hydrochloric Acid → methyl 4-[(2R)-2-({[(2R)-2-(6-amino-3-pyridinyl)-2-hydroxyethyl]amino}-methyl)-3,4-dihydro-2H-chromen-6-yl]benzoate

HRID 896902Notes

Reaction equation

[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C@@H:8]([OH:39])[CH2:9][N:10]([CH2:18][C@H:19]2[CH2:28][CH2:27][C:26]3[C:21](=[CH:22][CH:23]=[C:24]([C:29]4[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:31][CH:30]=4)[CH:25]=3)[O:20]2)C(OC(C)(C)C)=O)=[CH:4][CH:3]=1.Cl.O1CCOCC1>>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C@@H:8]([OH:39])[CH2:9][NH:10][CH2:18][C@H:19]2[CH2:28][CH2:27][C:26]3[C:21](=[CH:22][CH:23]=[C:24]([C:29]4[CH:30]=[CH:31][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:37][CH:38]=4)[CH:25]=3)[O:20]2)=[CH:4][CH:3]=1

Participants

Reactant 3

HCID 313Hydrochloric Acid

HCID 312751,4-Dioxane

HCID 59118207Methyl 4-((2R)-2-{[[(2R)-2-(6-amino-3-pyridinyl)-2-hydroxyethyl](tert-butoxycarbonyl)amino]methyl}-3,4-dihydro-2H-chromen-6-yl)benzoate

Product 1

HCID 59118232methyl 4-[(2R)-2-({[(2R)-2-(6-amino-3-pyridinyl)-2-hydroxyethyl]amino}-methyl)-3,4-dihydro-2H-chromen-6-yl]benzoateYield 62%

Procedure

Methyl 4-((2R)-2-{[[(2R)-2-(6-amino-3-pyridinyl)-2-hydroxyethyl](tert-butoxycarbonyl)-amino]methyl}-3,4-dihydro-2H-chromen-6-yl)benzoate (Example 377, 80 mg, 0.15 mmol) was added to 4 M hydrochloric acid in dioxane (3 mL, 12 mmol). The solution was stirred at room temperature for 18 hours and then concentrated in vacuo. The residue was purified by prep. HPLC, afforded 40 mg (62%) of the desired product. The product had: 1H NMR (CD3ODδ): 8.04 (d, J=8.1 Hz, 2 H), 7.89-8.03 (m, 2 H), 7.68 (d, J=7.8 Hz, 2 H), 7.42-7.49 (m, 2 H), 6.95-7.07 (m, 2 H), 5.02-5.10 (m, 1 H), 4.24-4.52 (m, 1 H), 3.91 (s, 3 H), 3.20-3.52 (m, 4 H), 2.81-3.04 (m, 2 H), 2.11-2.24 (m, 1 H), 1.74-1.92 (m, 1 H); mass spectroscopy gave m/z=434.2 [M+H]+ (calc'd exact mass for C25H27N3O4=433.2).

Workup

concentrationconcentrated in vacuo
customThe residue was purified by prep

Sources & evidence

ORD record: ord-85190f0540fd4266ae9e356e4d1cff94
Source dataset: uspto-grants-2005_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06919371B2

Reaction notes

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