4-Amino-3-fluorobenzoic acid → 4-amino-3-fluoro-N-(1-methyl-4-piperidyl)benzamide

HRID 2234381ノート

反応式

HRID 2234381 の反応式
[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[F:11].[NH2:12][CH:13]1[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CO.CN(C=O)C>[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:12][CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)=[O:8])=[CH:4][C:3]=1[F:11]

参加物

7

反応物 4

HCID 99714-Amino-3-fluorobenzoic acidHCID 81531DiisopropylethylamineHCID 27375314-Amino-1-methylpiperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

生成物 1

HCID 626798464-amino-3-fluoro-N-(1-methyl-4-piperidyl)benzamide

試薬・触媒・溶媒 2

HCID 887Methanol溶媒2 回HCID 6228Dimethylformamide溶媒

実験手順

4-Amino-3-Fluorobenzoic acid (Fluorochem; 1 g, 6.44 mmol), 4-Amino-1-methylpiperidine (Fluorochem; 811 mg, 7.09 mmol), HATU (2.70 g, 7.09 mmol), DIPEA (3.4 mL, 19.32 mmol) and DMF (15 mL) were combined and stirred for 18 hrs at room temperature. The solvent was evaporated and the resultant material dissolved in DCM (with a little MeOH to aid solubility) and chromatographed on silica eluting with a gradient of 0-10% 2M ammonia in MeOH/DCM. Fractions containing product were combined and evaporated to give an orange solid which was dissolved in MeOH and added to a 50 g SCX-2 column pre-wet with MeOH (2 column volumes). The column was flushed with MeOH (2 column volumes) and the product eluted with 2M ammonia in MeOH. Product containing fractions were evaporated to yield the title compound as a beige solid. (1.72 g, 100%)

後処理

  1. customThe solvent was evaporated
  2. dissolutionthe resultant material dissolved in DCM (with a little MeOH to aid solubility) and
  3. customchromatographed on silica eluting with a gradient of 0-10% 2M ammonia in MeOH/DCM
  4. additionFractions containing product
  5. customevaporated
  6. customto give an orange solid which
  7. customThe column was flushed with MeOH (2 column volumes)
  8. washthe product eluted with 2M ammonia in MeOH
  9. additionProduct containing fractions
  10. customwere evaporated

出典と根拠

ORDレコード
ord-fa97c1b401ad4a80a195e0a416e068f6
出典データセット
uspto-grants-2010_05
特許番号
US07709471B2

反応ノート

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