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

HRID 2085099
ノート
印刷プレビュー

反応式

HRID 2085099 の反応式
[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]=[C:19]([N:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)[N:18]=2)(=[O:15])=[O:14])=[CH:9][CH:8]=1)([CH3:6])([CH3:5])[CH3:4].[Br:44][C:45]1[CH:46]=[N:47][C:48](Cl)=[N:49][CH:50]=1>CN(C=O)C.C1COCC1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C(OCC)(=O)C>[C:3]([C:7]1[CH:8]=[CH:9][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:48]3[N:49]=[CH:50][C:45]([Br:44])=[CH:46][N:47]=3)[N:20]=[C:19]([N:38]3[CH2:39][CH2:40][O:41][CH2:42][CH2:43]3)[N:18]=2)(=[O:15])=[O:14])=[CH:11][CH:12]=1)([CH3:6])([CH3:4])[CH3:5]
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 3

HCID 24758Sodium hydrideHCID 6066655-Bromo-2-chloropyrimidineHCID 101885174-tert-Butyl-N-[6-(4-hydroxy-but-2-ynyloxy)-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yl]-benzenesulfonamide

生成物 1

HCID 101230844-tert.-butyl-N-[6-(4-(5-bromo-2-pyrimidinyloxy)-2-butynyloxy)-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yl]-benzene sulfonamide収率 94.5%

試薬・触媒・溶媒 3

HCID 311
Citric Acid
溶媒
HCID 8857Ethyl Acetate溶媒
HCID 21974620tetrahydrofuran N,N-dimethylformamide溶媒

実験手順

To a suspension of 9 mg of NaH 55% dispersion in mineral oil in 4 ml of DMF:THF 1:1 was added 50 mg of 4-tert.-butyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yl]-benzene sulfonamide (Example 14). After the evolution of gas had ceased, 42 mg of 5-bromo-2-chloropyrimidine was added and the mixture was stirred for 1 h at 650C before it was diluted with 50 ml of 10% aqueous citric acid and 50 ml of ethyl acetate. The organic layer was separated, washed with 50 ml of water, dried over MgSO4 and evaporated. The crude product was purified by column chromatography on silica gel eluting with hexane:ethyl acetate 3:2 to give 60 mg of 4-tert.-butyl-N-[6-(4-(5-bromo-2-pyrimidinyloxy)-2-butynyloxy)-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yl]-benzene sulfonamide as a colourless foam. MS: tR=6.14 min, [M+1]+=739.18, [M−1]+=741.32.

後処理

  1. customThe organic layer was separated
  2. washwashed with 50 ml of water
  3. dry with materialdried over MgSO4
  4. customevaporated
  5. customThe crude product was purified by column chromatography on silica gel eluting with hexane:ethyl acetate 3:2

出典と根拠

ORDレコード
ord-96da4313919245b4b7464cbd2c6e3625
出典データセット
uspto-grants-2004_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06720322B2

反応ノート

読み込み中…

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