Diisopropylethylamine → 4-amino-2,5-difluoro-N-[(3R)-1-methylpyrrolidin-3-yl]benzamide

HRID 2234496ノート

反応式

HRID 2234496 の反応式
[NH2:1][C:2]1[C:10]([F:11])=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([F:12])[CH:3]=1.Cl.Cl.[CH3:15][N:16]1[CH2:20][CH2:19][C@@H:18]([NH2:21])[CH2:17]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>CN(C=O)C>[NH2:1][C:2]1[C:10]([F:11])=[CH:9][C:5]([C:6]([NH:21][C@@H:18]2[CH2:19][CH2:20][N:16]([CH3:15])[CH2:17]2)=[O:8])=[C:4]([F:12])[CH:3]=1

参加物

6

反応物 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 201514774-Amino-2,5-difluorobenzoic acidHCID 53256048(3R)-1-Methyl-3-PyrrolidinaMine hydrochloride2 回

生成物 1

HCID 686824724-amino-2,5-difluoro-N-[(3R)-1-methylpyrrolidin-3-yl]benzamide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

4-amino-2,5-difluoro-benzoic acid (Rare Chemicals GmbH; 450 mg, 2.6 mmol), (3R)-1-methylpyrrolidin-3-amine di Hydrochloride (Intermediate 184; 473 mg, 2.73 mmol), HATU (1.08 g 2.86 mmol) and DIPEA (2.25 mL, 13 mmol) were combined in DMF (10 mL) and stirred at room temperature for 4 hours. The solvent was evaporated and the residue dissolved in MeOH and added to an SCX-2 column (20 g), pre-wet with MeOH (2 column volumes). The column was flushed with MeOH (2 column volumes) and eluted with 2M ammonia in MeOH. Product containing fractions were combined and evaporated and the resultant material dissolved in DCM and purified on a silica column eluting with 5% 2M ammonia in MeOH/DCM. Fractions containing product were combined and evaporated to a yellow gum. Diethylether was added and re-evaporated and dried under high vacuum to yield the title compound as a yellow gum, which slowly crystallised to a cream solid (550 mg, 83%)

後処理

  1. customThe solvent was evaporated
  2. dissolutionthe residue dissolved in MeOH
  3. additionadded to an SCX-2 column (20 g), pre-wet with MeOH (2 column volumes)
  4. customThe column was flushed with MeOH (2 column volumes)
  5. washeluted with 2M ammonia in MeOH
  6. additionProduct containing fractions
  7. customevaporated
  8. dissolutionthe resultant material dissolved in DCM
  9. custompurified on a silica column
  10. washeluting with 5% 2M ammonia in MeOH/DCM
  11. additionFractions containing product
  12. customevaporated to a yellow gum
  13. additionDiethylether was added
  14. customre-evaporated
  15. customdried under high vacuum

出典と根拠

ORDレコード
ord-328318b4be35479781975f95c2c99831
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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