Triethylamine → HCID 178472551, compound

HRID 2384039Notes

Reaction equation

HRID 2384039 reaction equation
[OH:1][C:2]1[N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[C:4]([C:11]([OH:13])=O)[N:3]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[CH2:37]([O:39][C:40](=[O:59])[C@H:41]([CH3:58])[CH2:42][C@H:43]([NH2:57])[CH2:44][C:45]1[CH:50]=[CH:49][C:48]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)=[CH:47][CH:46]=1)[CH3:38].C(N(CC)CC)C>CN(C=O)C.O>[C:48]1([C:51]2[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=2)[CH:47]=[CH:46][C:45]([CH2:44][C@@H:43]([NH:57][C:11]([C:4]2[N:3]=[C:2]([OH:1])[N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=2)=[O:13])[CH2:42][C@H:41]([C:40]([O:39][CH2:37][CH3:38])=[O:59])[CH3:58])=[CH:50][CH:49]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 25017086(2R,4S)-4-amino-5-(biphenyl-4-yl)-2-methylpentanoic acid ethyl ester hydrochloride2×HCID 1785245132-Hydroxypyrimidine-4,6-dicarboxylic acid

Product 1

HCID 178472551HCID 178472551, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2-hydroxypyrimidine-4,6-dicarboxylic acid (71 mg, 0.39 mmol) in DMF (10 mL) is added HOBT (59 mg, 0.39 mmol) and EDCl (74 mg, 0.39 mmol) and the mixture is stirred at room temperature for 10 minutes then (2R,4S)-4-amino-5-biphenyl-4-yl-2-methyl-pentanoic acid ethyl ester hydrochloride (Intermediate 1) (120 mg, 0.35 mmol) and triethylamine (0.15 ml, 1.16 mmol) are added. After stirring the mixture at room temperature for five hours, water is added and the mixture is extracted with ethyl acetate (3×). The combined organic layers are washed with water and brine then is dried over magnesium sulfate. The solvent is removed under reduced pressure and residue is purified by preparative HPLC using a gradient of 10% MeCN/water to 100% MeCN (0.1% TFA) to elute the title compound. HPLC retention time 1.32 minutes (condition C); MS 478.3 (M+H); 1H NMR (400 MHz, DMSO-d6): δ ppm 1.05-1.07 (d, J=7.07 Hz, 3H), 1.09-1.12 (t, J=7.07 Hz, 3H), 1.72-1.79 (m, 1H), 1.81-1.89 (m, 1H), 2.44-2.49 (m, 1H), 2.77-2.82 (m, 1H), 2.89-2.95 (m, 1H), 3.95-4.01 (q, J=7.07 Hz, 2H), 4.16-4.26 (m, 1H), 7.26-7.28 (m, 2H), 7.31-7.35 (m, 1H), 7.41-7.45 (m, 2H), 7.55-7.57 (m, 2H), 7.62-7.64 (m, 2H), 8.73-8.76 (d, J=9.35 Hz, 1H).

Workup

  1. stirringAfter stirring the mixture at room temperature for five hours
  2. extractionthe mixture is extracted with ethyl acetate (3×)
  3. washThe combined organic layers are washed with water and brine
  4. dry with materialthen is dried over magnesium sulfate
  5. customThe solvent is removed under reduced pressure and residue
  6. customis purified by preparative HPLC
  7. washto elute the title compound

Sources & evidence

ORD record
ord-8eb8b6932d774a3187f0d365dd41f5ca
Source dataset
uspto-grants-2012_09
Patent number
US08263629B2

Reaction notes

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