2,5-Pyridinediamine → Methyl 3-((6-aminopyridin-3-yl)carbamoyl)-4-methylbenzoate

HRID 453387Notes

Reaction equation

HRID 453387 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]([CH3:14])=[C:9]([CH:13]=1)[C:10]([OH:12])=O)=[O:4].CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC.[NH2:46][C:47]1[CH:52]=[CH:51][C:50]([NH2:53])=[CH:49][N:48]=1>ClCCl>[NH2:46][C:47]1[N:48]=[CH:49][C:50]([NH:53][C:10]([C:9]2[CH:13]=[C:5]([CH:6]=[CH:7][C:8]=2[CH3:14])[C:3]([O:2][CH3:1])=[O:4])=[O:12])=[CH:51][CH:52]=1

Participants

7

Reactant 5

HCID 203142,5-PyridinediamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 229994865-(Methoxycarbonyl)-2-methylbenzoic acid

Product 1

HCID 68453452Methyl 3-((6-aminopyridin-3-yl)carbamoyl)-4-methylbenzoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a round-bottomed flask was charged 5-(methoxycarbonyl)-2-methylbenzoic acid (0.2 g, 1.0 mmol), dicloromethane (3 ml), n,n-diisopropylethylamine (0.7 ml, 4.0 mmol), HOBt (0.16 g, 1.2 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.24 g, 1.2 mmol), and 2,5-diaminopyridine (0.11 g, 1.0 mmol) in that order. The reaction mixture was stirred at RT under N2 for 18 h. The reaction was partitioned between DCM (30 ml) and brine (20 mL). The aqueous layer was back extracted with DCM (3×15 mL) and the combined DCM layer was dried (Na2SO4) and concentrated. The crude product was dissolved in MeOH and absorbed on silica gel, pyrified by chromatography through a Redi-Sep 40 g column, eluting with a gradient of 0% to 10% MeOH in CH2Cl2, to provide methyl 3-((6-aminopyridin-3-yl)carbamoyl)-4-methylbenzoate as a tan solid. MS (ESI, pos. ion) m/z: 286.2 (M+1).

Workup

  1. customThe reaction was partitioned between DCM (30 ml) and brine (20 mL)
  2. extractionThe aqueous layer was back extracted with DCM (3×15 mL)
  3. dry with materialthe combined DCM layer was dried (Na2SO4)
  4. concentrationconcentrated
  5. dissolutionThe crude product was dissolved in MeOH
  6. customabsorbed on silica gel
  7. washeluting with a gradient of 0% to 10% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-de5888cc3dfe4f2991bdaf9e33e27356
Source dataset
uspto-grants-2013_07
Patent number
US08492404B2

Reaction notes

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