Sodium hydride → HCID 22729412, compound

HRID 2085095Notes

Reaction equation

HRID 2085095 reaction equation
[H-].[Na+].[C:3]([C:7]1[CH:12]=[CH:11][C:10]([S:13]([NH:16][C:17]2[C:22]([C:23]3[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=3)=[C:21]([O:30][CH2:31][C:32]#[C:33][CH2:34][OH:35])[N:20]=[CH:19][N:18]=2)(=[O:15])=[O:14])=[CH:9][CH:8]=1)([CH3:6])([CH3:5])[CH3:4].[Br:36][C:37]1[CH:38]=[N:39][C:40](Cl)=[N:41][CH:42]=1>C1COCC1>[C:3]([C:7]1[CH:8]=[CH:9][C:10]([S:13]([NH:16][C:17]2[C:22]([C:23]3[CH:24]=[CH:25][C:26]([CH3:29])=[CH:27][CH:28]=3)=[C:21]([O:30][C:31]#[C:32][CH2:33][CH2:34][O:35][C:40]3[N:41]=[CH:42][C:37]([Br:36])=[CH:38][N:39]=3)[N:20]=[CH:19][N:18]=2)(=[O:14])=[O:15])=[CH:11][CH:12]=1)([CH3:5])([CH3:4])[CH3:6]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 6066655-Bromo-2-chloropyrimidineHCID 10276651HCID 10276651, compound

Product 1

HCID 22729412HCID 22729412, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 88 mg of a 55% sodium hydride dispersion in mineral oil in 15 ml of dry THF 375 mg of 4-tert.-butyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(p-tolyl)-4-pyrimidinyl]-benzene sulfonamide (Example 12) was added. After stirring for 1 h, 170 mg of 5-bromo-2-chloropyrimidine was added. Stirring was continued for 60 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 containing a small amount of diethyl ether to give 168 mg of 4-tert.-butyl-N-[6-(4-(5-bromo-2-pyrimidinyloxy)-butynyloxy)-5-(p-tolyl)-4-pyrimidinyl]-benzene sulfonamide as beige crystals. LC-MS: tR=6.22 min, [M+1]+=624.28.

Workup

  1. additionwas added
  2. stirringStirring
  3. waitwas continued for 60 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 containing a small amount of diethyl ether

Sources & evidence

ORD record
ord-a461417118864361822d083e68b4cffc
Source dataset
uspto-grants-2004_04
Patent number
US06720322B2

Reaction notes

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