Sodium hydride → 4-tert.-butyl-N-[6-(4-(5-bromo-2-pyrimidinyloxy)-2-butynyloxy)-5-(o-methoxy-phenoxy)-4-pyrimidinyl]-benzene sulfonamide

HRID 2085096Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2085096
[H-].[Na+].[C:3]([C:7]1[CH:12]=[CH:11][C:10]([S:13]([NH:16][C:17]2[C:22]([O:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[O:30][CH3:31])=[C:21]([O:32][CH2:33][C:34]#[C:35][CH2:36][OH:37])[N:20]=[CH:19][N:18]=2)(=[O:15])=[O:14])=[CH:9][CH:8]=1)([CH3:6])([CH3:5])[CH3:4].[Br:38][C:39]1[CH:40]=[N:41][C:42](Cl)=[N:43][CH:44]=1>C1COCC1>[C:3]([C:7]1[CH:12]=[CH:11][C:10]([S:13]([NH:16][C:17]2[C:22]([O:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[O:30][CH3:31])=[C:21]([O:32][CH2:33][C:34]#[C:35][CH2:36][O:37][C:42]3[N:43]=[CH:44][C:39]([Br:38])=[CH:40][N:41]=3)[N:20]=[CH:19][N:18]=2)(=[O:14])=[O:15])=[CH:9][CH:8]=1)([CH3:6])([CH3:4])[CH3:5]

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 6066655-Bromo-2-chloropyrimidineHCID 101852334-tert-Butyl-N-[6-(4-hydroxy-but-2-ynyloxy)-5-(2-methoxy-phenoxy)-pyrimidin-4-yl]-benzenesulfonamide

Produkt 1

HCID 101684964-tert.-butyl-N-[6-(4-(5-bromo-2-pyrimidinyloxy)-2-butynyloxy)-5-(o-methoxy-phenoxy)-4-pyrimidinyl]-benzene sulfonamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a suspension of 29 mg of a 55% sodium hydride dispersion in mineral oil in 15 ml of dry THF 150 mg of 4-tert.-butyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(o-methoxy-phenoxy)-4-pyrimidinyl]-benzene sulfonamide (Example 10) was added. After stirring for 0.5 h, 64 mg of 5-bromo-2-chloropyrimidine was added. Stirring was continued for 40 h at 40° C. Eventually, the solvent was evaporated and the remaining residue was partitioned between 50 ml of 10% aqueous citric acid and 50 ml of ethyl acetate. The organic layer was separated and the aqueous layer was extracted two more times with 50 ml of ethyl acetate. The combined organic layers were washed with water and brine, dried over MgSO4 and evaporated. The crude product was crystallised from 2-propanol to give 126 mg of 4-tert.-butyl-N-[6-(4-(5-bromo-2-pyrimidinyloxy)-2-butynyloxy)-5-(o-methoxy-phenoxy)-4-pyrimidinyl]-benzene sulfonamide as beige crystals. LC-MS: tR=6.07 min, [M+1]+=656.24, [M−1]+=654.34.

Aufarbeitung

  1. additionwas added
  2. stirringStirring
  3. waitwas continued for 40 h at 40° C
  4. customEventually, the solvent was evaporated
  5. customthe remaining residue was partitioned between 50 ml of 10% aqueous citric acid and 50 ml of ethyl acetate
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was extracted two more times with 50 ml of ethyl acetate
  8. washThe combined organic layers were washed with water and brine
  9. dry with materialdried over MgSO4
  10. customevaporated
  11. customThe crude product was crystallised from 2-propanol

Quellen und Nachweise

ORD-Eintrag
ord-7c941751103940599932ea3dc70996f7
Quelldatensatz
uspto-grants-2004_04
Patentnummer
US06720322B2

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