Diisopropylethylamine → 1,1-Dimethylethyl {[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidine-3-yl]methyl}carbamate

HRID 1808967ノート

反応式

HRID 1808967 の反応式
[CH3:1][C:2]([O:5][C:6]([NH:8][CH2:9][C:10]1([OH:24])[CH2:13][N:12]([C:14]([O:16]CC2C=CC=CC=2)=O)[CH2:11]1)=[O:7])([CH3:4])[CH3:3].CCN(C(C)C)C(C)C.[F:34][C:35]1[C:36]([NH:45][C:46]2[CH:51]=[CH:50][C:49]([I:52])=[CH:48][C:47]=2[F:53])=[C:37]([CH:41]=[CH:42][C:43]=1[F:44])C(F)=O>[Pd].CO>[F:34][C:35]1[C:36]([NH:45][C:46]2[CH:51]=[CH:50][C:49]([I:52])=[CH:48][C:47]=2[F:53])=[C:37]([C:14]([N:12]2[CH2:11][C:10]([CH2:9][NH:8][C:6](=[O:7])[O:5][C:2]([CH3:1])([CH3:3])[CH3:4])([OH:24])[CH2:13]2)=[O:16])[CH:41]=[CH:42][C:43]=1[F:44]

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 594691583,4-Difluoro-2-(2-fluoro-4-iodoanilino)benzoyl fluorideHCID 67051555Benzyl 3-({[(tert-butoxy)carbonyl]amino}methyl)-3-hydroxyazetidine-1-carboxylate

生成物 1

HCID 685160531,1-Dimethylethyl {[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidine-3-yl]methyl}carbamate収率 66%

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 887Methanol溶媒

実験手順

Phenylmethyl 3-[({[(1,1-dimethylethyl)oxy]carbonyl}amino)methyl]-3-hydroxyazetidine-1-carboxylate (16.5 mg, 0.05 mmol) and 10% Pd/C (8 mg) were taken into methanol (2 mL) and hydrogenated at ambient pressure over 12 hours. The catalyst was removed by filtration and the filtrate concentrated and dried in vacuo. The residue was taken into THF (1 mL) followed by addition of DIPEA (10 μL, 0.06 mmol) and 3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzoyl fluoride (19.8 mg, 0.05 mmol), prepared using procedures similar to those described in Reference 1, and the solution was stirred at room temperature for 30 minutes. Concentration and purification of the residue by silica gel flash chromatography using hexanes:ethyl acetate (1:1.5) afforded 1,1-dimethylethyl {[1-({3,4-difluoro-2[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidine-3-yl]methyl}carbamate (19 mg, 66% yield).

後処理

  1. customThe catalyst was removed by filtration
  2. concentrationthe filtrate concentrated
  3. customdried in vacuo
  4. customprepared
  5. concentrationConcentration and purification of the residue by silica gel flash chromatography

出典と根拠

ORDレコード
ord-a36ab929ac974c4bad0556e7d63b839a
出典データセット
uspto-grants-2013_01
特許番号
US08362002B2

反応ノート

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