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

HRID 2100537노트

반응식

HRID 2100537 반응식
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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

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온도
90 °C

실험 절차

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−].

후처리

  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)

출처 및 근거

ORD 기록
ord-df511665f9934e72ace043c8266590db
출처 데이터셋
uspto-grants-2009_08
특허 번호
US07572801B2

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