Lithium hydroxide, monohydrate → HCID 10434480, compound

HRID 2355853Notes

Reaction equation

HRID 2355853 reaction equation
C(OC([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH2:17][CH:18]([C:39]([O:41]C)=[O:40])[NH:19][C:20]([N:22]3[CH2:27][CH2:26][CH:25]([N:28]4[CH2:37][C:36]5[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=5)[NH:30][C:29]4=[O:38])[CH2:24][CH2:23]3)=[O:21])=[CH:14][CH:15]=2)[CH:10]=[N:9]1)=O)(C)(C)C.O.[OH-].[Li+]>O1CCCC1.CO.O>[NH:8]1[C:16]2[C:11](=[CH:12][C:13]([CH2:17][CH:18]([NH:19][C:20]([N:22]3[CH2:27][CH2:26][CH:25]([N:28]4[CH2:37][C:36]5[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=5)[NH:30][C:29]4=[O:38])[CH2:24][CH2:23]3)=[O:21])[C:39]([OH:41])=[O:40])=[CH:14][CH:15]=2)[CH:10]=[N:9]1

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 58864391HCID 58864391, compound

Product 1

HCID 10434480HCID 10434480, compoundYield 80.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 5-(2-methoxycarbonyl-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-ethyl)-indazole-1-carboxylic acid tert-butyl ester (168 mg, 0.29 mmol) was dissolved in tetrahydrofuran (5 mL) in methanol (5 mL) was cooled to 0° C. A solution of lithium hydroxide monohydrate (49 mg, 2.04 mmol) in water (5 mL) was added. The reaction mixture was stirred at 0° C. for 6 h and then placed in the freezer for a further 16 h. The solvents were removed in vacuo and the residue dissolved in water (15 mL). The pH of the aqueous solution was adjusted to ca. 1 with 1N hydrochloric acid. The resulting white solid precipitated was collected by filtration. The solid was dried under vacuum to give the title compound (108 mg, 80%). 1H-NMR (DMSO-d6, 300 MHz) δ 12.94 (bs, 1H), 9.19 (s, 1H), 8.01 (s, 1H), 7.61 (s, 1H), 7.46 (d, J=8.4 Hz, 1H), 7.28 (dd, J=8.5, 1.5 Hz, 1H), 7.13-7.06 (m, 2H), 6.86 (t, J=7.0 Hz, 1H), 6.76-6.72 (m, 2H), 4.32-4.24 (m, 2H), 4.09-4.02 (m, 4H), 3.17-2.97 (m, 2H), 2.72-2.59 (m, 2H), 1.57-1.35 (m, 4H). IR (KBr, cm−1) 3424, 2963, 2930, 1660, 1628, 1505, 1474, 1446, 753. Mass spec.: 463 (MH)+.

Workup

  1. waitplaced in the freezer for a further 16 h
  2. customThe solvents were removed in vacuo
  3. dissolutionthe residue dissolved in water (15 mL)
  4. customThe resulting white solid precipitated
  5. filtrationwas collected by filtration
  6. customThe solid was dried under vacuum

Sources & evidence

ORD record
ord-f8e1c04ff9a743799b9fe5e472d1776a
Source dataset
uspto-grants-2010_07
Patent number
US07754732B2

Reaction notes

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