Diisopropylethylamine → HCID 86594198, 화합물

HRID 14152

반응식

HRID 14152 반응식
[Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([CH2:12][N:13]([CH2:15][CH2:16][CH2:17][CH3:18])[CH3:14])[CH:11]=1)[C:5]([O:7]C)=O.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[ClH:52].Cl.[NH2:54][C@@H:55]([CH2:71][C:72]1[CH:77]=[C:76]([F:78])[CH:75]=[C:74]([F:79])[CH:73]=1)[C@H:56]([OH:70])[CH2:57][NH:58][CH2:59][C:60]1[CH:65]=[CH:64][CH:63]=[C:62]([C:66]([F:69])([F:68])[F:67])[CH:61]=1>O1CCCC1.CO.O.O.[OH-].[Li+].C(OCC)(=O)C>[ClH:52].[ClH:52].[Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([CH2:12][N:13]([CH2:15][CH2:16][CH2:17][CH3:18])[CH3:14])[CH:11]=1)[C:5]([NH:54][C@@H:55]([CH2:71][C:72]1[CH:73]=[C:74]([F:79])[CH:75]=[C:76]([F:78])[CH:77]=1)[C@H:56]([OH:70])[CH2:57][NH:58][CH2:59][C:60]1[CH:65]=[CH:64][CH:63]=[C:62]([C:66]([F:67])([F:68])[F:69])[CH:61]=1)=[O:7]

참가 물질

8

반응물 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21086161Methyl 3-bromo-5-{[butyl(methyl)amino]methyl}benzoateHCID 57487373HCID 57487373, 화합물

생성물 1

HCID 86594198HCID 86594198, 화합물

시약·촉매·용매 3

HCID 8857Ethyl Acetate용매HCID 168937Lithium hydroxide, monohydrate용매HCID 21892291Methanol tetrahydrofuran water용매

실험 절차

Methyl 3-bromo-5-{[butyl(methyl)amino]methyl}benzoate prepared by the method in Example SP-190, Step 1 (200 mg, 0.64) is dissolved in 2:1:1 tetrahydrofuran/methanol/water (4 mL), and lithium hydroxide monohydrate is added (60 mg, 1.3 mmol), and the reaction stirred 16 h. The solution is concentrated under reduced pressure. The residue is redissolved in DMF (5 mL), and diisopropylethylamine (445 μL, 2.6 mmol), HATU (304 mg, 0.8 mmol), and (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-{[3-(trifluoromethyl)benzyl]amino}butan-2-ol dihydrochloride prepared by the method in Example S-2511 (315 mg, 0.7 mmol) are added. The reaction stirred at room temperature 16 h. The reaction mixture is diluted with ethyl acetate, washed with water, and saturated sodium bicarbonate, brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 9% methanol/methylene chloride) provides the title compound as the free base. The residue is dissolved in diethyl ether (3 mL) and 1N hydrochloric acid in diethyl ether (2 mL) is added. The mixture is concentrated under reduced pressure to yield the title compound. ESI MS m/z 656.2 [M+H]+.

후처리

  1. additionis added (60 mg, 1.3 mmol)
  2. concentrationThe solution is concentrated under reduced pressure
  3. dissolutionThe residue is redissolved in DMF (5 mL)
  4. additionare added
  5. stirringThe reaction stirred at room temperature 16 h
  6. washwashed with water, and saturated sodium bicarbonate, brine
  7. dry with materialdried (sodium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customPurification by flash column chromatography (silica, 9% methanol/methylene chloride)

출처 및 근거

ORD 기록
ord-246c6020d0774446a71de0b77a10a583
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07727997B2

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