1-Hydroxybenzotriazole → HCID 59608201, compound

HRID 2384044Notes

Reaction equation

HRID 2384044 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7]([OH:9])=O)=[CH:3][N:2]=1.C1C=CC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.C([O:47][C:48](=[O:67])[C@H:49]([CH3:66])[CH2:50][C@H:51]([NH2:65])[CH2:52][C:53]1[CH:58]=[CH:57][C:56]([C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)=[CH:55][CH:54]=1)C.CCN(C(C)C)C(C)C>CN(C=O)C.O>[C:56]1([C:59]2[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=2)[CH:55]=[CH:54][C:53]([CH2:52][C@@H:51]([NH:65][C:7]([C:4]2[CH:5]=[CH:6][N:1]=[N:2][CH:3]=2)=[O:9])[CH2:50][C@@H:49]([CH3:66])[C:48]([OH:67])=[O:47])=[CH:58][CH:57]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 2761046Pyridazine-4-carboxylic AcidHCID 25017086(2R,4S)-4-amino-5-(biphenyl-4-yl)-2-methylpentanoic acid ethyl ester hydrochloride

Product 1

HCID 59608201HCID 59608201, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of pyridazine-4-carboxylic acid (21 mg, 0.17 mmol) in DMF (6 mL) is added HOBT (26 mg, 0.17 mmol) and HBTU (65 mg, 0.17 mmol) and the mixture is stirred at room temperature for 10 minutes. (2R,4S)-4-Amino-5-biphenyl-4-yl-2-methyl-pentanoic acid ethyl ester hydrochloride (50 mg, 0.14 mmol) and DIEA (42 mg, 0.56 mmol) are added. After stirring the mixture at room temperature for 18 hours, water is added and the mixture is extracted three times with ethyl acetate. The combined organic layers are washed with water and brine then is dried over magnesium sulfate. The solvent is removed under reduced pressure to give the title compound; HPLC retention time 1.19 minutes (condition C); MS 390.3 (M+H); 1H NMR (400 MHz, DMSO-d6): δ ppm 1.08-1.10 (d, J=7.07 Hz, 3H), 1.59-1.66 (m, 1H), 1.88-1.95 (m, 1H), 2.46-2.53 (m, 1H), 2.85-2.87 (d, J=6.82 Hz, 2H), 4.22-4.30 (m, 1H), 7.29-7.32 (m, 2H), 7.33-7.36 (m, 1H), 7.42-7.46 (m, 2H), 7.57-7.59 (m, 2H), 7.62-7.65 (m, 2H), 7.91-7.93 (q, J=2.27 Hz, 1H), 8.76-8.78 (d, J=8.59 Hz, 1H), 9.41-9.43 (m, 1H), 9.45-9.46 (m, 1H), 12.09 (s, 1H).

Workup

  1. stirringAfter stirring the mixture at room temperature for 18 hours
  2. extractionthe mixture is extracted three times with ethyl acetate
  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

Sources & evidence

ORD record
ord-41304185506e40508a5752b9aa5ff5b5
Source dataset
uspto-grants-2012_09
Patent number
US08263629B2

Reaction notes

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