1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Ammonium

HRID 889213Notes

Reaction equation

HRID 889213 reaction equation
Cl.[CH3:2][NH:3][C:4]([C:6]1[CH:7]=[CH:8][C:9]([CH2:12][CH2:13][C:14]([OH:16])=O)=[N:10][CH:11]=1)=[O:5].C(N(C(C)C)C(C)C)C.[NH2:26][CH2:27][C:28]([N:30]([C:32]1[CH:37]=[CH:36][C:35]([Cl:38])=[C:34]([CH2:39][O:40][C:41]2[C:49]3[N:48]=[C:47]([O:50][CH3:51])[N:46]([CH2:52][C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][N:54]=4)[C:45]=3[CH:44]=[CH:43][CH:42]=2)[C:33]=1[Cl:59])[CH3:31])=[O:29].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>ClCCl>[NH4+:3].[Cl:59][C:33]1[C:34]([CH2:39][O:40][C:41]2[C:49]3[N:48]=[C:47]([O:50][CH3:51])[N:46]([CH2:52][C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][N:54]=4)[C:45]=3[CH:44]=[CH:43][CH:42]=2)=[C:35]([Cl:38])[CH:36]=[CH:37][C:32]=1[N:30]([CH3:31])[C:28](=[O:29])[CH2:27][NH:26][C:14](=[O:16])[CH2:13][CH2:12][C:9]1[CH:8]=[CH:7][C:6]([C:4]([NH:3][CH3:2])=[O:5])=[CH:11][N:10]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 66760013HCID 66760013, compoundHCID 667603852-amino-N-(2,4-dichloro-3-(((2-methoxy-1-(pyridin-2-ylmethyl)-1H-benzo[d]imidazol-4-yl)oxy)methyl)phenyl)-N-methylacetamide

Product 2

HCID 223AmmoniumYield 5%HCID 66760504HCID 66760504, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 3(5-methylcarbamoyl-pyridin-2-yl)propionic acid hydrochloride (0.26 g, 1.06 mmol) in dichloromethane (20 mL) was added ethyldiisopropylamine (0.74 mL, 4.26 mmol), the solution was stirred for 5 min, and then 2-amino-N-(2,4-dichloro-3-(((2-methoxy-1-(pyridin-2-ylmethyl)-1H-benzo[d]imidazol-4-yl)oxy)methyl)phenyl)-N-methylacetamide (0.5 g, 1.0 mmol) was added followed by HOBT (0.135 g, 1.0 mmol) and EDCI (0.28 mL, 1.59 mmol). The reaction mixture was then stirred overnight at room temperature and partitioned in dichloromethane (100 mL) and a saturated solution of NaHCO3 (100 mL). Organic layer was separated, dried (MgSO4) and concentrated to give oil, which was purified by flash chromatography using a mixture of dichloromethane- and a 5% ammonium solution in methanol (9:1) to give 6-(3-((2-((2,4-dichloro-3-(((2-methoxy-1-(pyridin-2-ylmethyl)-1H-benzo[d]imidazol-4-yl)oxy)methyl)phenyl)(methyl)amino)-2-oxoethyl)amino)-3-oxopropyl)-N-methylnicotinamide as foam. LCMS (APCI) 690 (M+); 1HNMR (400 MHz, MeOD) δ 2.60 (t, 2H), 3.07 (s, 3H), 3.19 (t, 2H), 3.20 (s, 3H), 3.32-3.69 (dd, 2H), 4.01 (s, 3H), 5.19 (s, 2H), 5.46 (dd, 2H), 6.71-8.74 (m, 12H)

Workup

  1. stirringThe reaction mixture was then stirred overnight at room temperature
  2. custompartitioned in dichloromethane (100 mL)
  3. customOrganic layer was separated
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customto give oil, which
  7. customwas purified by flash chromatography
  8. additiona mixture of dichloromethane-

Sources & evidence

ORD record
ord-f3833de0118f4c97a12296455d29be6e
Source dataset
uspto-grants-2012_08
Patent number
US08252793B2

Reaction notes

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