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Diisopropylethylamine → Methyl 3-[5-bromo-3-{[(1R,2R)-3-hydroxy-2-methyl-1-phenylpropyl]amino}-2-oxopyrazin-1(2H)-yl]-5-fluoro-4-methylbenzoate

HRID 337163
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인쇄 미리보기

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HRID 337163 반응식
Br[C:2]1[C:3](=[O:21])[N:4]([C:9]2[CH:10]=[C:11]([CH:16]=[C:17]([F:20])[C:18]=2[CH3:19])[C:12]([O:14][CH3:15])=[O:13])[CH:5]=[C:6]([Br:8])[N:7]=1.[NH2:22][C@@H:23]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C@@H:24]([CH3:27])[CH2:25][OH:26].CCN(C(C)C)C(C)C>C1COCC1.C(OCC)(=O)C>[Br:8][C:6]1[N:7]=[C:2]([NH:22][C@@H:23]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C@@H:24]([CH3:27])[CH2:25][OH:26])[C:3](=[O:21])[N:4]([C:9]2[CH:10]=[C:11]([CH:16]=[C:17]([F:20])[C:18]=2[CH3:19])[C:12]([O:14][CH3:15])=[O:13])[CH:5]=1
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참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 12452700(2R,3R)-3-Amino-2-methyl-3-phenylpropan-1-olHCID 66689945methyl 3-(3,5-dibromo-2-oxo-1(2H)-pyrazinyl)-5-fluoro-4-methylbenzoate

생성물 1

HCID 66690053Methyl 3-[5-bromo-3-{[(1R,2R)-3-hydroxy-2-methyl-1-phenylpropyl]amino}-2-oxopyrazin-1(2H)-yl]-5-fluoro-4-methylbenzoate

시약·촉매·용매 2

HCID 8028
Tetrahydrofuran
용매
HCID 8857Ethyl Acetate용매

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온도
50 °C

실험 절차

To methyl 3-(3,5-dibromo-2-oxopyrazin-1(2H)-yl)-5-fluoro-4-methylbenzoate (Example 252g, 0.9 g) in THF (3 mL) was added (2R,3R)-3-amino-2-methyl-3-phenylpropan-1-ol (Example 328a, 0.389 g) and Hunig's Base (0.374 mL) and the reaction stirred at 50° C. for 8 h. The reaction mixture was diluted with ethyl acetate and washed with aqueous NaHCO3. The organics were dried (MgSO4) and concentrated in vacuo to leave the crude product which was triturated overnight in 2:1 isohexane/diethyl ether to give the subtitle compound. Purification of the filtrate (SiO2 chromatography eluting with 50-100% diethyl ether in isohexane) to give further subtitle compound (total 0.820 g).

후처리

  1. washwashed with aqueous NaHCO3
  2. dry with materialThe organics were dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customto leave the crude product which
  5. customwas triturated overnight in 2:1 isohexane/diethyl ether

출처 및 근거

ORD 기록
ord-79d9149b3c9e4c1e9a605f43826e81f2
출처 데이터셋
uspto-grants-2014_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08889692B2

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