Hydrochloric Acid → (+/-)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2-[1,4']bipiperidinyl-1'-yl-1-(6-methoxy-pyridin-3-ylmethyl)-2-oxo-ethyl]-amide

HRID 2355907Notes

Reaction equation

HRID 2355907 reaction equation
C[O:2][C:3](=O)[CH:4]([NH:14][C:15]([N:17]1[CH2:22][CH2:21][CH:20]([N:23]2[CH2:32][C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[NH:25][C:24]2=[O:33])[CH2:19][CH2:18]1)=[O:16])[CH2:5][C:6]1[CH:7]=[N:8][C:9]([O:12][CH3:13])=[CH:10][CH:11]=1.O.[OH-].[Li+].Cl.[NH:39]1[CH2:44][CH2:43][CH:42]([N:45]2[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]2)[CH2:41][CH2:40]1.[PH2](Cl)=O>CO.O.C(Cl)Cl.C(N(CC)CC)C>[N:45]1([CH:42]2[CH2:43][CH2:44][N:39]([C:3](=[O:2])[CH:4]([NH:14][C:15]([N:17]3[CH2:22][CH2:21][CH:20]([N:23]4[CH2:32][C:31]5[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=5)[NH:25][C:24]4=[O:33])[CH2:19][CH2:18]3)=[O:16])[CH2:5][C:6]3[CH:7]=[N:8][C:9]([O:12][CH3:13])=[CH:10][CH:11]=3)[CH2:40][CH2:41]2)[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 786071,4'-BipiperidineHCID 168937Lithium hydroxide, monohydrateHCID 596396773-(6-methoxy-pyridin-3-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid methyl esterHCID 178527016HCID 178527016, compound

Product 1

HCID 11758340(+/-)-4-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carboxylic acid [2-[1,4']bipiperidinyl-1'-yl-1-(6-methoxy-pyridin-3-ylmethyl)-2-oxo-ethyl]-amide

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 3-(6-methoxy-pyridin-3-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid methyl ester (160 mg) in methanol (6 mL) was added a solution of lithium hydroxide monohydrate (29 mg) in water (1 mL). The reaction was stirred at room temperature for 4 h and cooled to 0° C. The reaction was treated with 1N hydrochloric acid (0.6 mL), concentrated. The residue obtained was dissolved in methylene chloride (5 mL), and treated sequentially with 4-piperidyl-piperidine (75 mg), triethylamine (0.14 mL), and bis-2-oxo-3-oxazolidinyl)phosphinic chloride (104 mg). The reaction was stirred overnight, concentrated, and purified by prep HPLC to give 94 mg (45%). LC/MS: tR=1.86 min, 604.51 (MH)+.

Workup

  1. temperaturecooled to 0° C
  2. concentrationconcentrated
  3. customThe residue obtained
  4. stirringThe reaction was stirred overnight
  5. concentrationconcentrated
  6. custompurified by prep HPLC
  7. customto give 94 mg (45%)

Sources & evidence

ORD record
ord-a67dd3ce406b4a60a361c3711c37c56d
Source dataset
uspto-grants-2010_07
Patent number
US07754732B2

Reaction notes

Loading…