1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-(4-Aminobenzyl)-3-(3-(3-hydroxyphenyl)-1-morpholino-1-oxopropan-2-yl)urea

HRID 1397877Notes

Reaction equation

HRID 1397877 reaction equation
C(OC([NH:8][C:9]1[CH:31]=[CH:30][C:12]([CH2:13][NH:14][C:15](=[O:29])[NH:16][CH:17]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[CH:23]=2)[C:18]([OH:20])=O)=[CH:11][CH:10]=1)=O)(C)(C)C.[OH:32][C:33]1[C:41]2[N:40]=NNC=2C=CC=1.[CH:42](N(C(C)C)CC)(C)[CH3:43].CN(C)CCCN=C=NCC>CN(C=O)C>[NH2:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:13][NH:14][C:15]([NH:16][CH:17]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[CH:23]=2)[C:18]([N:40]2[CH2:41][CH2:33][O:32][CH2:43][CH2:42]2)=[O:20])=[O:29])=[CH:30][CH:31]=1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 683345852-(3-(4-(Tert-butoxycarbonylamino)benzyl)ureido)-3-(3-hydroxyphenyl) propanoic acidHCID 178418300HCID 178418300, compound

Product 1

HCID 672582161-(4-Aminobenzyl)-3-(3-(3-hydroxyphenyl)-1-morpholino-1-oxopropan-2-yl)ureaYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Acid derivative 175 (1 equivalent) was dissolved in 2 ml of DMF. Amine (1.1 equivalent), Hydroxybenzotriazole (HOBO (1.2 equivalent), diisopropylethylamine (DIEA) (2.2 equivalent) and 1-[3-(Dimethylamino)propyl]-3-ethylcarbodiimide (EDAP) (1.2 equivalent) were added successively and the reaction mixture is stirred for 20 h at room temperature. The reaction mixture is concentrated and 100 ml of AcOEt are added. The organic phase are washed with NaHCO3 saturated, 10% citric acid and brine then dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography (AcOEt) to afford the amide as white solid (80 mg, 73%). 1H NMR (DMSO): δ 1.48 (s, 9H), 1.60 (m, 2H), 1.72 (m, 2H), 2.62 (m, 1H), 2.80 (dd, 1H, J=13.4, 5.2 Hz), 3.77 (m, 2H), 3.98 (m, 2H), 4.08 (d, 2H, J=5.3 Hz), 4.90 (m, 1H), 6.14 (d, 1H, J=8.8 Hz), 6.43 (t, 1H, J=5.3 Hz), 6.60 (m, 3H), 7.05 (d, 1H, J=8.5 Hz), 7.08 (d, 2H, J=8.2 Hz), 7.36 (d, 2H, J=8.2 Hz), 9.25 (s, 1H), 9.27 (s, 1H). The protected urea (78 mg) was dissolved in 2 μl of DCM and 2 ml of TFA was added then the reaction mixture was let 1 h at room temperature. The reaction mixture was concentrated and purified by precipitation using AcOEt/Hexane to afford the urea deprotected 176 as yellow solid (75 mg, 92%). HPLC method B tr=15.77 mn (92.3%). ESI-MS m/z: 399.4 [M+H]+.

Workup

  1. concentrationThe reaction mixture is concentrated
  2. addition100 ml of AcOEt are added
  3. washThe organic phase are washed with NaHCO3 saturated, 10% citric acid and brine
  4. dry with materialthen dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by flash chromatography (AcOEt)

Sources & evidence

ORD record
ord-11ae7ba634414409934aa2e8bd733f83
Source dataset
uspto-grants-2014_12
Patent number
US08901295B2

Reaction notes

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