1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 89704805, compound

HRID 928962Notes

Reaction equation

HRID 928962 reaction equation
[F:1][C:2]1[C:7]2[N:8]=[CH:9][O:10][C:6]=2[CH:5]=[C:4]([C:11]([OH:13])=O)[C:3]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18]([I:21])=[CH:17][C:16]=1[F:22].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[CH:44]([O:46][CH2:47][CH2:48][O:49][NH2:50])=[CH2:45].[NH4+].[Cl-]>C(Cl)Cl>[F:1][C:2]1[C:7]2[N:8]=[CH:9][O:10][C:6]=2[CH:5]=[C:4]([C:11]([NH:50][O:49][CH2:48][CH2:47][O:46][CH:44]=[CH2:45])=[O:13])[C:3]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18]([I:21])=[CH:17][C:16]=1[F:22]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 89704789HCID 89704789, compound

Product 1

HCID 89704805HCID 89704805, compoundYield 99.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-fluoro-5-((2-fluoro-4-iodophenyl)amino)benzo[d]oxazole-6-carboxylic acid (500 mg, 1.2 mmol) in CH2Cl2 was added HOBt (254 mg, 1.63 mmol) and EDCI (314 mg, 1.63 mmol). The mixture was stirred for 1 h and O-(2-(vinyloxy)ethyl)hydroxylamine (172 mg, 1.62 mmol) was added. After stirring for 4 h at ambient temperature, the reaction was treated with saturated NH4Cl (aq., 20 mL). The resultant mixture was extracted with CH2Cl2 (30 mL×3). The combined organic extracts were washed with water (30 mL×2) and brine (30 mL) sequentially, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (CH2Cl2/MeOH, 20:1, v/v) and gave the desired product (white solid, 598 mg, 98% yield). 1H NMR (400 MHz, DMSO-d6): δ 11.82 (s, 1H), 8.96 (s, 1H), 8.01 (s, 1H), 7.88 (s, 1H), 7.53 (d, J=10.8 Hz, 1H), 7.28 (d, J=8.1 Hz, 1H), 6.50 (dd, J=13.9, 6.6 Hz, 1H), 6.40 (d, J=6.0 Hz, 1H), 4.18 (d, J=14.5 Hz, 1H), 3.99 (m, 3H), 3.83 (s, 2H).

Workup

  1. stirringAfter stirring for 4 h at ambient temperature
  2. extractionThe resultant mixture was extracted with CH2Cl2 (30 mL×3)
  3. washThe combined organic extracts were washed with water (30 mL×2) and brine (30 mL) sequentially
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography on silica gel (CH2Cl2/MeOH, 20:1, v/v)

Sources & evidence

ORD record
ord-b5aef8e766394573a7d863923ea4eb22
Source dataset
uspto-grants-2016_03
Patent number
US09290468B2

Reaction notes

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