Diisopropylethylamine → (6-Fluoro-4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-ylmethyl)-carbamic acid benzyl ester

HRID 2100537ノート

反応式

HRID 2100537 の反応式
F[C:2]1[N:10]=[CH:9][C:8]([F:11])=[CH:7][C:3]=1[C:4]([OH:6])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.[CH2:43]([O:50][C:51](=[O:57])[NH:52][CH2:53][C:54](=[NH:56])[NH2:55])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>CN(C=O)C.ClCCl>[CH2:43]([O:50][C:51](=[O:57])[NH:52][CH2:53][C:54]1[NH:56][C:4](=[O:6])[C:3]2[CH:7]=[C:8]([F:11])[CH:9]=[N:10][C:2]=2[N:55]=1)[C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 244144Benzyl 2-amino-2-iminoethylcarbamateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 118159992,5-difluoropyridine-3-carboxylic Acid

生成物 1

HCID 136368392(6-Fluoro-4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-ylmethyl)-carbamic acid benzyl ester収率 22%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
90 °C

実験手順

2,5-Difluoronicotinic acid (547 mg, 3.44 mmol), TBTU (1.33 g, 4.14 mmol) and DIPEA (3.40 ml, 19.85 mmol) were added to a solution of carbamimidoylmethyl-carbamic acid benzyl ester [77390-81-9] (725 mg, 3.51 mmol) in DMF (20 ml). The solution was stirred for 5 hours at ambient temperature and 30 hours at 90° C. The brown suspension was poured onto ice cold aqueous buffer solution pH5/dichloromethane 1/1. The layers were separated, the aqueous layer was extracted twice with dichloromethane, the combined extracts were washed with brine and dried over magnesium sulfate. Removal of the solvent under reduced pressure and crystallization (EtOAc/TBME) yielded (6-fluoro-4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-ylmethyl)-carbamic acid benzyl ester (250 mg, 0.757 mmol; 22%) as white solid. MS: m/e=327.1 [M−H−].

後処理

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted twice with dichloromethane
  3. washthe combined extracts were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. customRemoval of the solvent
  6. customunder reduced pressure and crystallization (EtOAc/TBME)

出典と根拠

ORDレコード
ord-df511665f9934e72ace043c8266590db
出典データセット
uspto-grants-2009_08
特許番号
US07572801B2

反応ノート

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