Triethylamine → N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-2-(3-(1-methyl-1H-pyrazol-5-yl)phenyl)acetamide

HRID 1777152Notes

Reaction equation

HRID 1777152 reaction equation
[CH3:1][N:2]1[C:6]([C:7]2[CH:8]=[C:9]([CH2:13][C:14]([OH:16])=O)[CH:10]=[CH:11][CH:12]=2)=[CH:5][CH:4]=[N:3]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC.[NH2:45][CH2:46][CH:47]([OH:59])[CH2:48][N:49]1[CH2:58][CH2:57][C:56]2[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=2)[CH2:50]1>C(Cl)Cl.O>[CH2:50]1[C:51]2[C:56](=[CH:55][CH:54]=[CH:53][CH:52]=2)[CH2:57][CH2:58][N:49]1[CH2:48][CH:47]([OH:59])[CH2:46][NH:45][C:14](=[O:16])[CH2:13][C:9]1[CH:10]=[CH:11][CH:12]=[C:7]([C:6]2[N:2]([CH3:1])[N:3]=[CH:4][CH:5]=2)[CH:8]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 167907201-amino-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-olHCID 902414232-[3-(2-Methylpyrazol-3-yl)phenyl]aceticacid

Product 1

HCID 90241691N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-2-(3-(1-methyl-1H-pyrazol-5-yl)phenyl)acetamideYield 21.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(3-(1-methyl-1H-pyrazol-5-yl)phenyl)acetic acid (150 mg, 0.69 mmol) in DCM (6 mL) was added EDCI (265 mg, 1.38 mmol), HOBt (186 mg, 1.38 mmol), Et3N (209 mg, 2.07 mmol) and 1-amino-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol (142 mg, 0.69 mmol). The mixture was stirred at room temperature for 16 h then diluted with water (10 mL) and extracted with DCM (10 mL x 3). The combined organic layers were concentrated. The residue was purified by prep-HPLC to give the product as a colorless oil (60 mg, Yield 21%). 1H NMR (400 MHz, MeOD): 7.47 (s, 1H), 7.43-7.33 (m, 4H), 7.08-7.04 (m, 3H), 6.96-6.94 (m, 1H), 6.35 (s, 1H), 3.96-3.91 (m, 1H), 3.83 (s, 3H), 3.60-3.59 (m, 4H), 3.38-3.20 (m, 2H), 2.84 (t, J=6.0 Hz, 2H), 2.72 (t, J=6.0 Hz, 2H), 2.49 (d, J=6.4 Hz, 2H). LCMS (m/z): 405.2 (M+1).

Workup

  1. extractionextracted with DCM (10 mL x 3)
  2. concentrationThe combined organic layers were concentrated
  3. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-b0b605e93c4943d0b41621b893ba85bf
Source dataset
uspto-grants-2016_02
Patent number
US09266836B2

Reaction notes

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