Sodium Hydroxide → (+/-)-3-[2-(4-Hydroxy-piperidin-1-yl)-thiazol-4-yl]-3-[4-(7-methoxy-quinolin-8-yl)-[1,4]diazepan-1-yl]-propionic acid methyl ester

HRID 532838Notes

Reaction equation

HRID 532838 reaction equation
[N:1]1([C:8]2[C:9]([O:18][CH3:19])=[CH:10][CH:11]=[C:12]3[C:17]=2[N:16]=[CH:15][CH:14]=[CH:13]3)[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[OH:20][CH:21]1[CH2:26][CH2:25][N:24]([C:27]2[S:28][CH:29]=[C:30]([CH:32]=O)[N:31]=2)[CH2:23][CH2:22]1.C([Si]([O:41][C:42]([O:44][CH3:45])=[CH2:43])(C)C)(C)(C)C.C([O-])(O)=O.[Na+].[OH-].[Na+]>C(Cl)Cl.ClCCCl>[CH3:45][O:44][C:42](=[O:41])[CH2:43][CH:32]([C:30]1[N:31]=[C:27]([N:24]2[CH2:23][CH2:22][CH:21]([OH:20])[CH2:26][CH2:25]2)[S:28][CH:29]=1)[N:4]1[CH2:5][CH2:6][CH2:7][N:1]([C:8]2[C:9]([O:18][CH3:19])=[CH:10][CH:11]=[C:12]3[C:17]=2[N:16]=[CH:15][CH:14]=[CH:13]3)[CH2:2][CH2:3]1

Participants

8

Reactant 5

HCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 45644911-(tert-Butyldimethylsilyloxy)-1-methoxyetheneHCID 593661612-(4-Hydroxy-piperidin-1-yl)-thiazole-4-carbaldehydeHCID 593661628-(1,4-Diazepan-1-yl)-7-methoxyquinoline

Product 1

HCID 59366202(+/-)-3-[2-(4-Hydroxy-piperidin-1-yl)-thiazol-4-yl]-3-[4-(7-methoxy-quinolin-8-yl)-[1,4]diazepan-1-yl]-propionic acid methyl esterYield 38%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
55 °C

Procedure

1,2-Dichloroethane (1.02 mL) was added to a mixture of 8-[1,4]diazepan-1-yl-7-methoxy-quinoline (1.00 g, 3.88 mmol) and 2-(4-hydroxy-piperidin-1-yl)-thiazole-4-carbaldehyde (824 mg, 3.88 mmol). The reaction was heated to 55° C. and stirred until homogeneous. Freshly crushed Ti(OMe)4 (1.00 g, 5.82 mmol) was then added and the reaction was stirred at 55° C. for 1 h. tert-Butyl-(1-methoxy-vinyloxy)-dimethyl-silane (1.02 mL, 4.66 mmol) was then added and the reaction was stirred at 55° C. for 18 h. CH2Cl2 was then added, followed by sat. aq. NaHCO3, then 1 N aq. NaOH. This mixture was then stirred for 5 min and filtered through celite, washing the filter cake with CH2Cl2. The filtrate was then washed once with H2O, dried over MgSO4, filtered, and concentrated. The crude product was purified on silica gel (99:1 to 90:10 CH2Cl2:(9:1 MeOH:NH4OH)) to give the product (660 mg, 38% yield).

Workup

  1. additionwas then added
  2. stirringthe reaction was stirred at 55° C. for 18 h
  3. stirringThis mixture was then stirred for 5 min
  4. filtrationfiltered through celite
  5. washwashing the filter cake with CH2Cl2
  6. washThe filtrate was then washed once with H2O
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified on silica gel (99:1 to 90:10 CH2Cl2:(9:1 MeOH:NH4OH))

Sources & evidence

ORD record
ord-2254de526a4342c0baf15f2cc23136b7
Source dataset
uspto-grants-2014_10
Patent number
US08853202B2

Reaction notes

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