Lithium Hydroxide → (+)-3-(7-methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid

HRID 2355862Notes

Reaction equation

HRID 2355862 reaction equation
C[O:2][C:3](=[O:36])[CH:4]([NH:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([N:25]2[CH2:34][C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[NH:27][C:26]2=[O:35])[CH2:21][CH2:20]1)=[O:18])[CH2:5][C:6]1[CH:7]=[C:8]2[C:12](=[C:13]([CH3:15])[CH:14]=1)[NH:11][N:10]=[CH:9]2.O1CCCC1.CO.[OH-].[Li+]>O>[CH3:15][C:13]1[CH:14]=[C:6]([CH2:5][CH:4]([NH:16][C:17]([N:19]2[CH2:20][CH2:21][CH:22]([N:25]3[CH2:34][C:33]4[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=4)[NH:27][C:26]3=[O:35])[CH2:23][CH2:24]2)=[O:18])[C:3]([OH:36])=[O:2])[CH:7]=[C:8]2[C:12]=1[NH:11][N:10]=[CH:9]2

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 21899815MeOH tetrahydrofuranHCID 24862915(+/-)-3-(7-Methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid methyl ester

Product 1

HCID 21102025(+)-3-(7-methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acidYield 75%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A suspension of (±)-3-(7-methyl-1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid methyl ester (240.0 mg, 0.489 mmol) in 1:1 tetrahydrofuran/methanol (20 mL) at room temperature was treated with a solution of lithium hydroxide (140.5 mg, 7 equiv) in water (10 mL). Within 1 min, the mixture became homogeneous and it was left to stand at 4° C. overnight. The solvents were evaporated at ca. 30° C. and the pH was adjusted to ca. 1 with 1N hydrochloric acid. The resulting white suspension was stored at 4° C. for several hours and the product was collected by filtration, washed with a small amount of water, and dried in vacuo (169.0 mg, 73%). Solid sodium chloride was added to the filtrate resulting in precipitation of more product (5.2 mg, total yield 75%). 1H-NMR (CD3OD, 500 MHz) δ 1.2-1.7 (4H, m), 2.58 (3H, s), 2.5-3.2 (4H, m), 3.35 (2H, m), 4.15 (2H, m), 4.36 (1H, m), 4.60 (1H, m), 6.79 (1H, d), 6.96 (1H, t), 7.18 (3H, m), 7.49 (1H, s), 8.00 (1H, s). Mass spec.: 477.13 (MH)+.

Workup

  1. waitit was left
  2. waitto stand at 4° C. overnight
  3. customThe solvents were evaporated at ca. 30° C.
  4. waitThe resulting white suspension was stored at 4° C. for several hours
  5. filtrationthe product was collected by filtration
  6. washwashed with a small amount of water
  7. customdried in vacuo (169.0 mg, 73%)
  8. additionSolid sodium chloride was added to the filtrate
  9. customresulting in precipitation of more product (5.2 mg, total yield 75%)

Sources & evidence

ORD record
ord-a0290342f5f547e59090077591144e66
Source dataset
uspto-grants-2010_07
Patent number
US07754732B2

Reaction notes

Loading…