2-Dimethylaminopyridine → HCID 178499660, compound

HRID 460735Notes

Reaction equation

HRID 460735 reaction equation
[CH:1]1([C:7]2[C:12](=[O:13])[N:11]3[N:14]=[C:15]([C:17](O)=[O:18])[CH:16]=[C:10]3[NH:9][C:8]=2[C:20]2[O:21][CH:22]=[CH:23][CH:24]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:25]([N:28]([CH:31]([CH3:33])[CH3:32])CC)([CH3:27])[CH3:26].CN([C:37]1[CH:42]=[CH:41]C=CN=1)C.Cl.[CH3:44][O:45][C:46](=[O:59])[C@H:47](CC1C2C(=CC=CC=2)NC=1)[NH2:48].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O.C(OCC)(=O)C>[CH3:44][O:45][C:46](=[O:59])[CH:47]([NH:48][C:17]([C:15]1[CH:16]=[C:10]2[NH:9][C:8]([C:20]3[O:21][CH:22]=[CH:23][CH:24]=3)=[C:7]([CH:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)[C:12](=[O:13])[N:11]2[N:14]=1)=[O:18])[CH2:33][C:31]1[NH:28][C:25]2[C:26]([CH:32]=1)=[CH:41][CH:42]=[CH:37][CH:27]=2

Participants

8

Reactant 5

HCID 218852-DimethylaminopyridineHCID 81531DiisopropylethylamineHCID 2734891Methyl tryptophanate hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178524066HCID 178524066, compound

Product 1

HCID 178499660HCID 178499660, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 8.2 mg (0.025 mmol) of 6-cyclohexyl-5-furan-2-yl-7-oxo-4,7-dihydro-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid in 2 mL of dimethylformamide (DMF) was added 0.009 mL (0.05 mmol) of diisopropylethylamine (DIEA), a few crystals of dimethylaminopyridine (DMAP cat), 7 mg (0.027 mmol) of L-tryptophan methyl ester hydrochloride, followed by 11 mg (0.03 mmol) of HATU, and the resulting mixture was stirred at rt overnight. The reaction mixture was diluted with ethyl acetate, washed with 0.1 N sodium hydroxide solution (2 times) and brine. The separated organic layer was dried over sodium sulfate and concentrated to give a residue which was purified via reverse-phase chromatography (Gilson) to afford desired 2-[(6-cyclohexyl-5-furan-2-yl-7-oxo-4,7-dihydro-pyrazolo[1,5-a]pyrimidine-2-carbonyl)-amino]-3-(1H-indol-2-yl)-propionic acid methyl ester (606). This compound was then converted to 2-[(6-cyclohexyl-5-furan-2-yl-7-oxo-4,7-dihydro-pyrazolo[1,5-a]pyrimidine-2-carbonyl)-amino]-3-(1H-indol-2-yl)-propionic acid (599) via the well known LiOH saponification protocol (39% yield over 2 steps); LC-MS calcd. for C28H27N5O5 [M++H]+: 514.2; found: 514.2.

Workup

  1. washwashed with 0.1 N sodium hydroxide solution (2 times) and brine
  2. dry with materialThe separated organic layer was dried over sodium sulfate
  3. concentrationconcentrated
  4. customto give a residue which
  5. customwas purified via reverse-phase chromatography (Gilson)

Sources & evidence

ORD record
ord-84e2886be21f4bc6a03ad4e1e9519913
Source dataset
uspto-grants-2007_03
Patent number
US07196111B2

Reaction notes

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