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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-(6,7-difluoro-1H-benzimidazol-1-yl)acetamide

HRID 420003
ノート
印刷プレビュー

反応式

HRID 420003 の反応式
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[CH:8][N:7]([CH2:10][C:11]([OH:13])=O)[C:6]=2[C:14]=1[F:15].[NH2:16][CH:17]([C:19]1[CH:24]=[CH:23][C:22]([C:25]([CH3:29])([CH3:28])[C:26]#[N:27])=[CH:21][C:20]=1[CH3:30])[CH3:18].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.[OH-].[Na+]>[C:26]([C:25]([C:22]1[CH:23]=[CH:24][C:19]([CH:17]([NH:16][C:11](=[O:13])[CH2:10][N:7]2[C:6]3[C:14]([F:15])=[C:2]([F:1])[CH:3]=[CH:4][C:5]=3[N:9]=[CH:8]2)[CH3:18])=[C:20]([CH3:30])[CH:21]=1)([CH3:28])[CH3:29])#[N:27]
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57939018(6,7-difluoro-1H-benzimidazol-1-yl)acetic acidHCID 582984892-[4-(1-Aminoethyl)-3-methylphenyl]-2-methylpropanenitrile

生成物 1

HCID 24850175N-{1-[4-(1-cyano-1-methylethyl)-2-methylphenyl]ethyl}-2-(6,7-difluoro-1H-benzimidazol-1-yl)acetamide収率 75%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 6228Dimethylformamide溶媒HCID 14798Sodium Hydroxide溶媒

実験手順

To a solution of (6,7-difluoro-1H-benzimidazol-1-yl)acetic acid (250 mg, 1.18 mmol) prepared according to scheme 2, 2-[4-(1-aminoethyl)-3-methylphenyl]-2-methylpropanenitrile (202 mg 1.18 mmol) prepared according to scheme 15 and DMAP (285 mg, 2.35 mmol) stirred in anhydrous DMF (4.0 mL) is added HATU (448 mg, 1.18 mmol) after 18 hours of stirring, the mixture is diluted with 1N NaOH (40.0 mL) and then extracted 4 times with EtOAc (4×40.0 mL). The organic phases are combined and dried over MgSO4. The mixture is filtered and concentrated. The product is purified on a preparative LCMS system equipped with a Synergi Polar (4u) 21.2×50 mm column, mobile phase: A=water (ammonium carbonate buffer 0.01 M), B=MeCN using a short 40 to 60% B 10 min. gradient high pH method. The pure fractions are combined then extracted with ethyl acetate which is separated dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to provide the expected product N-{1-[4-(1-cyano-1-methylethyl)-2-methylphenyl]ethyl}-2-(6,7-difluoro-1H-benzimidazol-1-yl)acetamide (350 mg, 75%) as a white solid. 1H NMR (400 MHz, METHANOL-D4) d ppm 1.44 (d, J=6.84 Hz, 3H) 1.66 (s, 6H) 2.36 (s, 3H) 5.06 (d, J=16.99 Hz, 1H) 5.11 (d, J=16.99 Hz, 1H) 5.20 (q, J=7.03 Hz, 1H) 7.14 (ddd, J=11.38, 8.84, 7.52 Hz, 1H) 7.26 (d, J=2.15 Hz, 1H) 7.32 (dd, J=6.05, 2.15 Hz, 1H) 7.37-7.43 (m, 2H) 8.09 (s, 1H). MS [M+H], calcd: 397.2. found: 397.3. The enantiomers are separated on a chiral OD column, using methanol and CO2 as the mobile phase.

後処理

  1. customprepared
  2. extractionextracted 4 times with EtOAc (4×40.0 mL)
  3. dry with materialdried over MgSO4
  4. filtrationThe mixture is filtered
  5. concentrationconcentrated
  6. customThe product is purified on a preparative LCMS system
  7. customequipped with a Synergi Polar (4u) 21.2×50 mm column, mobile phase
  8. customa short 40 to 60% B 10 min.
  9. extractionThe pure fractions are combined then extracted with ethyl acetate which
  10. customis separated
  11. dry with materialdried over anhydrous Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-6362fed949454790bc00e26ae04f8703
出典データセット
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08093402B2

反応ノート

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このページの内容参加物実験手順後処理出典と根拠反応ノート