Lithium Hydroxide → HCID 10230069, compound

HRID 890407Notes

Reaction equation

[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12]([CH:14]([NH:21][C:22]([C:24]2[CH:33]=[C:32](Cl)[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:25]=2)=[O:23])[CH2:15][CH2:16][C:17]([O:19]C)=[O:18])=[O:13])[CH2:8][CH2:7]1)=[O:5])[CH3:2].[OH:35][C@@H:36]1[CH2:41][CH2:40]C[NH:38][CH2:37]1.CCN(C(C)C)C(C)C.[OH-].[Li+]>CS(C)=O>[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12]([CH:14]([NH:21][C:22]([C:24]2[CH:33]=[C:32]([N:38]3[CH2:40][CH2:41][CH:36]([OH:35])[CH2:37]3)[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:25]=2)=[O:23])[CH2:15][CH2:16][C:17]([OH:19])=[O:18])=[O:13])[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 110 °C

Procedure

To a solution of 2-[1-(4-(ethoxycarbonyl)piperazin-1-yl)carbonyl-3-(methoxycarbonyl)propyl]aminocarbonyl-4-chloroquinoline (150 mg, 0.315 mmol) in DMSO (3.0 mL) was added (R)-3-hydroxypiperidine (68 mg, 0.5 mmol) and DIEA (65 mg, 0.5 mL). The mixture was heated at 110° C. for 18 hours. The crude reaction mixture was treated with lithium hydroxide (3.0 mL 0.25 M) for 4 hours. The reaction was purified by preparative HPLC to afford 2-[1-(4-(ethoxycarbonyl)piperazin-1-yl)carbonyl-3-carboxypropyl]aminocarbonyl-4-(3-hydroxypyrrolidin-1-yl)quinoline (41.0 mg); NMR (DMSO-d6) 1.2 (t, 3), 2.00–2.20 (m, 4), 2.45 (m, 2), 3.30–3.75 (m, 8), 4.05 (q, 2), 4.60 (s, 1), 5.11 (m, 1), 7.39 (s, 1), 7.65 (m, 1), 7.95 (m, 1), 8.28 (m, 1), 8.58 (br s, 1), 9.75 (m, 1) ppm.

Workup

customThe crude reaction mixture
customThe reaction was purified by preparative HPLC

Sources & evidence

ORD record: ord-333d48e7131d4ce6b051b36ec9c47d9c
Source dataset: uspto-grants-2006_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06995156B2

Reaction notes

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