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Aniline → HC-030031

HRID 44417
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Reaction equation

HRID 44417 reaction equation
[N:1]1([C:12](=[O:13])[C:11]2[N:10]([CH2:14][C:15]([OH:17])=O)[CH:9]=[N:8][C:7]=2[N:5]([CH3:6])[C:3]1=[O:4])[CH3:2].CCN(C(C)C)[CH:21]([CH3:23])[CH3:22].[NH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.CCN=C=NCCCN(C)C>CN(C=O)C.CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:2][N:1]1[C:12](=[O:13])[C:11]2[N:10]([CH2:14][C:15]([NH:27][C:28]3[CH:33]=[CH:32][C:31]([CH:21]([CH3:23])[CH3:22])=[CH:30][CH:29]=3)=[O:17])[CH:9]=[N:8][C:7]=2[N:5]([CH3:6])[C:3]1=[O:4]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 6115AnilineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 69550AcefyllineHCID 81531Diisopropylethylamine

Product 1

HCID 1150897HC-030031Yield 41%

Reagents, catalysts & solvents 3

HCID 14284
4-(Dimethylamino)pyridine
Catalyst
HCID 6228DimethylformamideSolvent
HCID 6344DichloromethaneSolvent

Procedure

To the suspension of theophylline-7-acetic acid (101, 32.5 g, 0.136 mol) in anhydrous DMF (400 mL), was added DIPEA (54 mL, 0.31 mol) at 0° C. The neat aniline (102, 20.4 mL, 0.143 mol) was added followed by addition of DMAP (19.2 g, 0.16 mol) and EDCI (30.1 g, 0.16 mol). The reaction mixture was warmed to room temperature over 18 h, then stirred at 40-43° C. for 1.5 days. The reaction mixture was diluted with CH2Cl2 (1.8 L), washed with H2O (0.7 L), 10% citric acid (0.5 L), NaHCO3 (saturated, 0.6 L), brine, dried over Na2SO4 and concentrated in vacuo and crystallized from ethyl acetate/hexanes to yield compound 200 (41%, 19.8 g): MS (APCI) m/z: 356.2 [M+H]+. Anal. Calcd. for C18H21N5O3: C, 60.83; H, 5.96; N, 19.71. Found: C, 60.53; H, 5.97; N, 19.76.

Workup

  1. washwashed with H2O (0.7 L), 10% citric acid (0.5 L), NaHCO3 (saturated, 0.6 L), brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customcrystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-ce3ea129c544445ab7e1ab343833eaf5
Source dataset
uspto-grants-2013_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08541423B2

Reaction notes

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