1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 6-Chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (1-dimethylcarbamoyl-2-phenylethyl)amide

HRID 1693490Notes

Reaction equation

HRID 1693490 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]2[CH:8]=[C:9]([C:11]([OH:13])=O)[NH:10][C:4]=2[CH:3]=1.Cl.[NH2:15][C@@H:16]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]([N:19]([CH3:21])[CH3:20])=[O:18].CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>CN(C=O)C>[CH3:21][N:19]([CH3:20])[C:17]([CH:16]([NH:15][C:11]([C:9]1[NH:10][C:4]2[CH:3]=[C:2]([Cl:1])[N:7]=[CH:6][C:5]=2[CH:8]=1)=[O:13])[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:18]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 12653778(2S)-2-Amino-N,N-dimethyl-3-phenylpropanamide hydrochlorideHCID 378189746-chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid

Product 1

HCID 729534216-Chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (1-dimethylcarbamoyl-2-phenylethyl)amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (Preparation 116, 47 mg, 0.24 mmol) in DMF (5 mL, anhydrous) was added 2-(S)-amino-N,N-dimethyl-3-phenylpropionamide hydrochloride (Preparation 8, 56 mg, 0.25 mmol), DIPEA (131 μL, 0.75 mmol) and HOBt (40 mg, 0.26 mmol) sequentially. The solution was stirred for 5 min prior to the addition of EDCI (55 mg, 0.29 mmol) in one portion. The resulting solution was stirred for 12 h at rt. The reaction mixture was partitioned between ethyl acetate (50 mL) and water/brine (150 mL, 1:1). The layers were separated and the aqueous phase extracted with ethyl acetate (3×50 mL), then the combined organics were washed with dilute HCl solution (1M, 50 mL), dilute NaOH solution (1M, 50 mL) and brine (50 mL). The organic phase was dried (MgSO4), filtered and concentrated in vacuo. Purification via flash column chromatography eluting with toluene/acetone (3:1) gave the title compound. δH (CDCl3): 2.88, 3.05 (6H, 2s), 3.18, 3.28 (2H, 2 dd), 5.41 (2H, m), 7.02 (1H, s), 7.28-7.34 (6H, m), 8.17 (1H, d), 8.68 (1H, s), 10.58 (1H, br s); m/z (ES+)=371.13 [M+H]+; RT=3.28 min.

Workup

  1. stirringThe resulting solution was stirred for 12 h at rt
  2. customThe reaction mixture was partitioned between ethyl acetate (50 mL) and water/brine (150 mL, 1:1)
  3. customThe layers were separated
  4. extractionthe aqueous phase extracted with ethyl acetate (3×50 mL)
  5. washthe combined organics were washed with dilute HCl solution (1M, 50 mL), dilute NaOH solution (1M, 50 mL) and brine (50 mL)
  6. dry with materialThe organic phase was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification via flash column chromatography
  10. washeluting with toluene/acetone (3:1)

Sources & evidence

ORD record
ord-a7e5b4bd971e4e2a9d1b630be0d18b89
Source dataset
uspto-grants-2012_04
Patent number
US08158622B2

Reaction notes

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