Diisopropylethylamine → (2R,4R)-4-[(5-Acetyl-2H-pyrazole-3-carbonyl)amino]-5-biphenyl-4-yl-2-hydroxypentanoic Acid Ethyl Ester

HRID 2045136Notes

Reaction equation

HRID 2045136 reaction equation
[CH2:1]([O:3][C:4](=[O:23])[C@H:5]([OH:22])[CH2:6][C@H:7]([NH2:21])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)[CH3:2].[C:24]([C:27]1[CH:28]=[C:29]([C:32](O)=[O:33])[NH:30][N:31]=1)(=[O:26])[CH3:25].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:23])[C@H:5]([OH:22])[CH2:6][C@H:7]([NH:21][C:32]([C:29]1[NH:30][N:31]=[C:27]([C:24](=[O:26])[CH3:25])[CH:28]=1)=[O:33])[CH2:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)=[CH:13][CH:14]=1)[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 167673463-acetyl-1H-pyrazole-5-carboxylic acidHCID 67969400(2R,4R)-4-amino-5-biphenyl-4-yl-2-hydroxypentanoic acid ethyl ester

Product 1

HCID 57377879(2R,4R)-4-[(5-Acetyl-2H-pyrazole-3-carbonyl)amino]-5-biphenyl-4-yl-2-hydroxypentanoic Acid Ethyl EsterYield 66.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(2R,4R)-4-Amino-5-biphenyl-4-yl-2-hydroxypentanoic acid ethyl ester (HCl salt; 500 mg, 1 mmol, 1.0 eq.), 5-acetyl-2H-pyrazole-3-carboxylic acid (330.4 mg, 2.1 mmol, 1.5 eq.), and HATU (820 mg, 2.1 mmol, 1.5 eq.) were combined in DMF (5 mL), and the resulting mixture was stirred for 2 minutes. DIPEA (750 μL) was added and the mixture was stirred for 1 hour. The mixture was dried under vacuum, and the product was purified using reverse phase chromatography (10-70% MeCN/H2O; 0.05% TFA over 70 minutes) to yield the title compound (300 mg, purity 98%) as a TFA salt. MS m/z [M+H]+ calc'd for C25H27N3O5, 450.20. found 450.2.

Workup

  1. stirringthe mixture was stirred for 1 hour
  2. customThe mixture was dried under vacuum
  3. customthe product was purified
  4. customphase chromatography (10-70% MeCN/H2O; 0.05% TFA over 70 minutes)

Sources & evidence

ORD record
ord-22cf86a938e54911a45445575a147cfb
Source dataset
uspto-grants-2013_11
Patent number
US08586536B2

Reaction notes

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