Benzyl Bromide → 4-tert.-butyl-N-[6-(4-benzyloxy-2-butynyloxy)-5-(o-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl]benzene sulfonamide

HRID 2085107Notes

Reaction equation

HRID 2085107 reaction equation
[CH2:1]([O:8][CH2:9][C:10]#[C:11][CH2:12][OH:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)C#CCO.C(Br)C1C=CC=CC=1.[H-].[Na+].[C:30]([C:34]1[CH:39]=[CH:38][C:37]([S:40]([NH:43][C:44]2[C:49]([O:50][C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=3[O:57][CH3:58])=[C:48](Cl)[N:47]=[C:46]([C:60]3[N:65]=[CH:64][CH:63]=[CH:62][N:61]=3)[N:45]=2)(=[O:42])=[O:41])=[CH:36][CH:35]=1)([CH3:33])([CH3:32])[CH3:31]>CN(C=O)C.C1COCC1.C(OCC)(=O)C>[NH3:43].[C:30]([C:34]1[CH:39]=[CH:38][C:37]([S:40]([NH:43][C:44]2[C:49]([O:50][C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=3[O:57][CH3:58])=[C:48]([O:13][CH2:12][C:11]#[C:10][CH2:9][O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[N:47]=[C:46]([C:60]3[N:65]=[CH:64][CH:63]=[CH:62][N:61]=3)[N:45]=2)(=[O:42])=[O:41])=[CH:36][CH:35]=1)([CH3:33])([CH3:31])[CH3:32]

Participants

9

Reactant 5

HCID 7498Benzyl BromideHCID 80662-Butyne-1,4-diolHCID 24758Sodium hydrideHCID 110303484-Benzyloxy-2-butyn-1-olHCID 111351604-Tert-butyl-n-(6-chloro-5-(2-methoxyphenoxy)-2,2'-bipyrimidin-4-yl)benzenesulfonamide

Product 2

HCID 222AmmoniaHCID 101224954-tert.-butyl-N-[6-(4-benzyloxy-2-butynyloxy)-5-(o-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl]benzene sulfonamideYield 79%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 390 mg of 4-benzyloxy-2-butyn-1-ol (prepared starting from 2-butyn-1,4-diol and benzylbromide in analogy to a procedure reported in Tetrahedron Left. 38 (1997), 7887-7890) in 5 ml DMF:THF 1:1 was added 97 mg of 55% NaH in mineral oil. After the evolution of gas had ceased, 250 mg of 4-tert.-butyl-N-[6-chloro-5-(o-methoxyphenoxy)-2-(2-pyrimidinyl)4-pyrimidinyl]benzene sulfonamide (Example 5a) was added and the mixture was stirred at 50° C. for 20 h before it was diluted with 75 ml of ethyl acetate. The mixture was washed with 75 ml of 10% aqueous citric acid and 75 ml of water, and evaporated. The crude product was purified by chromatography on prep. tlc-plates with ethyl acetate:methanol:sat. aqueous ammonia 10:2:1 to give 125 mg of 4-tert.-butyl-N-[6-(4-benzyloxy-2-butynyloxy)-5-(o-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl]benzene sulfonamide as a yellow foam. LC-MS: tR=5.93 min, [M+1]+=666.47, [M−1]−=664.63.

Workup

  1. waitLeft
  2. washThe mixture was washed with 75 ml of 10% aqueous citric acid and 75 ml of water
  3. customevaporated
  4. customThe crude product was purified by chromatography on prep

Sources & evidence

ORD record
ord-f237c14d43fe4c0fac036fe29a17586e
Source dataset
uspto-grants-2004_04
Patent number
US06720322B2

Reaction notes

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