1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 68312971, compound

HRID 1530640Notes

Reaction equation

HRID 1530640 reaction equation
[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[N:11]([CH2:12][CH2:13][O:14][C:15]4[CH:22]=[C:21]([O:23][C:24]([CH3:29])([CH3:28])[C:25]([OH:27])=O)[CH:20]=[CH:19][C:16]=43)[CH:10]=2)=[N:7][C:6]([CH3:30])=[N:5]1)([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.[CH3:40][N:41]1[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>CN(C=O)C>[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[C:16]4[CH:19]=[CH:20][C:21]([O:23][C:24]([CH3:29])([CH3:28])[C:25]([N:44]5[CH2:45][CH2:46][N:41]([CH3:40])[CH2:42][CH2:43]5)=[O:27])=[CH:22][C:15]=4[O:14][CH2:13][CH2:12][N:11]3[CH:10]=2)=[N:7][C:6]([CH3:30])=[N:5]1)([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide2×HCID 531671-MethylpiperazineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 68312906HCID 68312906, compound

Product 1

HCID 68312971HCID 68312971, compoundYield 61.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 2-[2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-8-yloxy]-2-methylpropionic acid from Example 45 (0.0922 mmol) in DMF (2 mL) were added DIPEA (47 ul, 0.277 mmol), 1-methylpiperazine (31 uL, 0.277 mmol), HOBt (19 mg, 0.138 mmol) and EDCI (27 mg, 0.138 mmol) and the reaction mixture was stirred at RT for 2 h. Additional EDCI (50 mg) was added and the reaction mixture was stirred at RT for 18 h. The mixture was then partitioned between EtOAc and water. The aqueous layer was further extracted with EtOAc and the combined organic layers were washed with water, followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 2-8% MeOH in DCM) affording 250 as a white solid (28 mg, 60% over three steps). LCMS: RT 2.92 min [M+H]+ 494.1. 1H NMR (DMSO, 400 MHz): δ 8.29 (1H, d, J=8.97 Hz), 7.83 (1H, s), 6.64 (1H, dd, J=8.98, 2.60 Hz), 6.42 (1H, d, J=2.57 Hz), 5.88-5.76 (1H, m), 4.47 (4H, s), 3.75-3.44 (4H, m), 2.24 (3H, s), 2.19 (2H, s), 2.06-1.94 (5H, m), 1.58 (6H, s), 1.44 (6H, d, J=6.59 Hz)

Workup

  1. stirringthe reaction mixture was stirred at RT for 18 h
  2. customThe mixture was then partitioned between EtOAc and water
  3. extractionThe aqueous layer was further extracted with EtOAc
  4. washthe combined organic layers were washed with water
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 2-8% MeOH in DCM)

Sources & evidence

ORD record
ord-880150639bcc4777b31f5ed3f5c8b6aa
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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