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Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → (-)-N-{1-[4-(1-cyano-1-methylethyl)-2-methylphenyl]ethyl}-2-(7-fluoro-1H-benzimidazol-1-yl)acetamide

HRID 420005
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HRID 420005 반응식
[F:1][C:2]1[C:7]2[N:8]([CH2:11][C:12]([OH:14])=O)[CH:9]=[N:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.[NH2:15][CH:16]([C:18]1[CH:23]=[CH:22][C:21]([C:24]([CH3:28])([CH3:27])[C:25]#[N:26])=[CH:20][C:19]=1[CH3:29])[CH3:17].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C1C=CN=CC=1)C.CN(C=O)C.CO>[C:25]([C:24]([C:21]1[CH:22]=[CH:23][C:18]([CH:16]([NH:15][C:12](=[O:14])[CH2:11][N:8]2[C:7]3[C:2]([F:1])=[CH:3][CH:4]=[CH:5][C:6]=3[N:10]=[CH:9]2)[CH3:17])=[C:19]([CH3:29])[CH:20]=1)([CH3:27])[CH3:28])#[N:26]
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참가 물질

7

반응물 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 112177812-(7-Fluoro-1H-1,3-benzodiazol-1-yl)acetic acidHCID 582984892-[4-(1-Aminoethyl)-3-methylphenyl]-2-methylpropanenitrile

생성물 1

HCID 24850221(-)-N-{1-[4-(1-cyano-1-methylethyl)-2-methylphenyl]ethyl}-2-(7-fluoro-1H-benzimidazol-1-yl)acetamide수율 63%

시약·촉매·용매

3
HCID 142844-(Dimethylamino)pyridine촉매HCID 887Methanol용매HCID 6228Dimethylformamide용매

실험 절차

To a solution of (7-fluoro-1H-benzimidazol-1-yl)acetic acid (250 mg, 1.29 mmol) prepared according to scheme 5, 2-[4-(1-aminoethyl)-3-methylphenyl]-2-methylpropanenitrile (260 mg 1.29 mmol) prepared according to scheme 15 and DMAP (156 mg, 1.29 mmol) stirred in anhydrous DMF (4.0 mL) is added HATU (490 mg, 1.29 mmol) after 18 hours of stirring, the mixture is diluted with Methanol (200 μL) the solution is purified directly on a preparative LCMS system equipped with a Synergi Polar (4u) 21.2×50 mm column, mobile phase: A=water (0.1% TFA), B=MeCN using a short 40 to 60% B 10 min. gradient method. The pure fractions are combined the TFA neutralized with a 4N NaOH solution and then extracted with ethyl acetate which is separated dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to provide the expected product (+) and (−)-N-{1-[4-(1-cyano-1-methylethyl)-2-methylphenyl]ethyl}-2-(7-fluoro-1H-benzimidazol-1-yl)acetamide (306 mg, 63%) as a white solid. 1H NMR (400 MHz, METHANOL-D4) δ ppm 1.44 (d, J=6.84 Hz, 3H) 1.66 (s, 6H) 2.35 (s, 3H) 5.02-5.14 (m, 2H) 5.19 (q, J=7.03 Hz, 1H) 6.99 (dd, J=11.52, 7.42 Hz, 1H) 7.19 (dt, J=8.15, 4.98 Hz, 1H) 7.26 (d, J=2.15 Hz, 1H) 7.32 (dd, J=8.01, 2.34 Hz, 3H) 7.39 (d, J=8.20 Hz, 1H) 7.45 (d, J=7.62 Hz, 1H) 8.09 (s, 1H), MS [M+H], calcd: 379.2. found: 379.2.

후처리

  1. customprepared
  2. customis purified directly on a preparative LCMS system
  3. customequipped with a Synergi Polar (4u) 21.2×50 mm column, mobile phase
  4. customa short 40 to 60% B 10 min. gradient method
  5. extractionextracted with ethyl acetate which
  6. customis separated
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-ea8bcd636f09482db2e3fde401bf8f82
출처 데이터셋
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08093402B2

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