1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → tert-butyl 4-((1S)-1-{[(2,5-dichloropyridin-3-yl)carbonyl]amino}ethyl)benzoate

HRID 1293183

反応式

HRID 1293183 の反応式
[Cl:1][C:2]1[N:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:3]=1[C:4]([OH:6])=O.[NH2:12][C@H:13]([C:15]1[CH:27]=[CH:26][C:18]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[CH:17][CH:16]=1)[CH3:14].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1>ClCCl.C(N(CC)CC)C>[Cl:1][C:2]1[C:3]([C:4]([NH:12][C@H:13]([C:15]2[CH:27]=[CH:26][C:18]([C:19]([O:21][C:22]([CH3:24])([CH3:23])[CH3:25])=[O:20])=[CH:17][CH:16]=2)[CH3:14])=[O:6])=[CH:7][C:8]([Cl:11])=[CH:9][N:10]=1

参加物

7

反応物 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27360852,5-Dichloropyridine-3-carboxylic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 51358470tert-butyl 4-[(1S)-1-aminoethyl]benzoate

生成物 1

HCID 57572256tert-butyl 4-((1S)-1-{[(2,5-dichloropyridin-3-yl)carbonyl]amino}ethyl)benzoate収率 70%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8471Triethylamine溶媒

実験手順

To a stirred solution of 2,5-dichloronicotinic acid (Syn. Commun. 1989, 19, 553–9, 1.92 g, 10 mmol) and tert-butyl 4-[(1S)-1-aminoethyl]benzoate (example 44 step 3, 2.02 g, 9.1 mmol) in dichloromethane (20 mL) were successively added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (2.59 g, 13.5 mmol), 1-hydroxybenzotriazole hydrate (HOBT) (2.07 g, 13.5 mmol), and triethylamine (4 mL). After being stirred overnight, the reaction was quenched by the addition of saturated sodium bicarbonate aqueous solution (100 mL). The aqueous layer was extracted with dichloromethane (50 mL×3) and the combined organic layers were washed with brine (100 mL), dried (sodium sulfate), and evaporated. The remaining residue was purified by flush column chromatography on silica gel (100 g) eluting with dichloromethane/ethyl acetate (20/1) to afford 2.51 g (70%) of the title compounds as white solids: 1H-NMR (CDCl3) δ 8.41 (1H, d, J=2.6 Hz), 8.09 (1H, d, J=2.6 Hz), 7.99 (2H, d, J=8.3 Hz), 7.43 (2H, d, J=8.3 Hz), 6.81 (1H, d, J=7.2 Hz), 5.33 (1H, dq, J=7.2, 7.0 Hz), 1.62 (3H, d, J=7.0 Hz), 1.58 (9H, s).

後処理

  1. customthe reaction was quenched by the addition of saturated sodium bicarbonate aqueous solution (100 mL)
  2. extractionThe aqueous layer was extracted with dichloromethane (50 mL×3)
  3. washthe combined organic layers were washed with brine (100 mL)
  4. dry with materialdried (sodium sulfate)
  5. customevaporated
  6. customThe remaining residue was purified
  7. customby flush column chromatography on silica gel (100 g)
  8. washeluting with dichloromethane/ethyl acetate (20/1)

出典と根拠

ORDレコード
ord-197a03deed514e97bd29a962f9aa3629
出典データセット
uspto-grants-2007_07
特許番号
US07238714B2

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