1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-2-((1-methyl-1H-benzo[d]imidazol-5-yl)oxy)acetamide

HRID 1429462Notes

Reaction equation

[CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][C:9]([O:11][CH2:12][C:13]([OH:15])=O)=[CH:10][C:5]=2[N:4]=[CH:3]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[NH2:37][CH2:38][CH:39]([OH:51])[CH2:40][N:41]1[CH2:50][CH2:49][C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH2:42]1>CN(C=O)C>[CH2:42]1[C:43]2[C:48](=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH2:49][CH2:50][N:41]1[CH2:40][CH:39]([OH:51])[CH2:38][NH:37][C:13](=[O:15])[CH2:12][O:11][C:9]1[CH:8]=[CH:7][C:6]2[N:2]([CH3:1])[CH:3]=[N:4][C:5]=2[CH:10]=1

Participants

Conditions

Temperature: 29 °C

Procedure

To a solution of 2-((1-methyl-1H-benzo[d]imidazol-5-yl)oxy)acetic acid (160 mg, 0.776 mmol) in DMF (4 ml) was added TEA (336 mg, 3.33 mmol), HOBt (157 mg, 1.164 mmol), EDCI (223 mg, 1.164 mmol) and 1-amino-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol (192 mg, 0.931 mmol) at 29° C. The reaction mixture was stirred for 16 h at 29° C. until TLC showed the reaction to be complete. After evaporation of the solvent, the mixture was purified by preparative HPLC to give the title compound (13.1 mg, 4.2%) as colorless oil. 1H NMR (400 MHz, MeOD) δ 8.05 (s, 1H), 7.45 (d, J=8.8 Hz, 1H), 7.21 (d, J=2.0 Hz, 1H), 7.09-6.97 (m, 5H), 4.59 (s, 2H), 4.03-3.97 (m, 1H), 3.84 (s, 3H), 3.65 (dd, J1=14.8 Hz, J2=30.4 Hz, 2H), 3.47-3.42 (m, 2H), 2.88 (t, J=5.6 Hz, 2H), 2.72 (t, J=5.6 Hz, 2H), 2.53-2.51 (m, 2H). LCMS (m/z): 395.2 (M+1).

Workup

customthe reaction
customAfter evaporation of the solvent
customthe mixture was purified by preparative HPLC

Sources & evidence

ORD record: ord-2cff3914e0eb433fab3f4169f9051d9b
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940726B2

Reaction notes

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