Hydrochloric Acid → HCID 58864337, compound

HRID 2355854Notes

Reaction equation

HRID 2355854 reaction equation
C[O:2][C:3](=[O:44])[C@H:4]([NH:24][C:25]([N:27]1[CH2:32][CH2:31][CH:30]([N:33]2[CH2:42][C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[NH:35][C:34]2=[O:43])[CH2:29][CH2:28]1)=[O:26])[CH2:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([S:15]([CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])(=[O:17])=[O:16])[N:10]=[CH:9]2.O.[OH-].[Li+].Cl>O1CCCC1.CO.O>[O:43]=[C:34]1[N:33]([CH:30]2[CH2:29][CH2:28][N:27]([C:25]([NH:24][C@H:4]([CH2:5][C:6]3[CH:7]=[C:8]4[C:12](=[CH:13][CH:14]=3)[N:11]([S:15]([CH2:18][CH2:19][Si:20]([CH3:21])([CH3:23])[CH3:22])(=[O:17])=[O:16])[N:10]=[CH:9]4)[C:3]([OH:44])=[O:2])=[O:26])[CH2:32][CH2:31]2)[CH2:42][C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[NH:35]1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 58864519HCID 58864519, compound

Product 1

HCID 58864337HCID 58864337, compoundYield 90.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (R)-2-{[4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-3-[1-(2-trimethylsilanyl-ethanesulfonyl)-1H-indazol-5-yl]-propionic acid methyl ester (775 mg, 1.21 mmol) in tetrahydrofuran (9 mL) and methanol (3 mL) was cooled to 0° C. A solution of lithium hydroxide monohydrate (115 mg, 4.84 mmol) in water (3 mL) was added. The reaction mixture was stirred at 0° C. for 2 h and then placed in the freezer at −15° C. for 16 h. While cooling the reaction mixture with an ice bath, the pH was increased to ca. 7 by addition of 1N hydrochloric acid (3.8 mL). Organic solvents were removed under vacuum. The resulting aqueous solution was extracted with ethyl acetate after addition of more 1N hydrochloric acid (0.5 mL). The combined extracts were dried over magnesium sulfate, filtered and evaporated to give 684 mg (90%) of the title compound as a white solid. 1H-NMR (DMSO-d6, 300 MHz) δ 9.21 (s, 1H), 8.58 (s, 1H), 7.90 (d, J=8.4 Hz, 1H), 7.78 (s, 1H), 7.56 (d, J=8.1 Hz, 1H), 7.13-7.09 (m, 2H), 6.88-6.83 (m, 1H), 6.76-6.74 (m, 2H), 4.33-4.27 (m, 2H), 4.18 (s, 2H), 4.09-3.96 (m, 3H), 3.57-3.51 (m, 2H), 3.25-3.04 (m, 2H), 2.74-2.60 (m, 2H), 1.54-1.43 (m, 4H), 0.70-0.64 (m, 2H), −0.08 (s, 9H). Mass spec.: 627 (MH)+.

Workup

  1. waitplaced in the freezer at −15° C. for 16 h
  2. temperatureWhile cooling the reaction mixture with an ice bath
  3. customOrganic solvents were removed under vacuum
  4. extractionThe resulting aqueous solution was extracted with ethyl acetate
  5. additionafter addition of more 1N hydrochloric acid (0.5 mL)
  6. dry with materialThe combined extracts were dried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-2d10b4f64839431884e4fc340738c9ed
Source dataset
uspto-grants-2010_07
Patent number
US07754732B2

Reaction notes

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