Diisopropylethylamine → 1-(2-Hydroxy-2-methyl-propyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid [4-(2-phenyl-furo[3,2-b]pyridin-7-yloxy)-phenyl]-amide

HRID 1470358Notes

Reaction equation

HRID 1470358 reaction equation
[OH:1][C:2]([CH3:21])([CH3:20])[CH2:3][N:4]1[C:8]([CH3:9])=[C:7]([C:10]([OH:12])=O)[C:6](=[O:13])[N:5]1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.C(N(CC)C(C)C)(C)C.[C:46]1([C:52]2[O:60][C:59]3[C:54](=[N:55][CH:56]=[CH:57][C:58]=3[O:61][C:62]3[CH:68]=[CH:67][C:65]([NH2:66])=[CH:64][CH:63]=3)[CH:53]=2)[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1>O1CCOCC1>[C:46]1([C:52]2[O:60][C:59]3[C:54](=[N:55][CH:56]=[CH:57][C:58]=3[O:61][C:62]3[CH:63]=[CH:64][C:65]([NH:66][C:10]([C:7]4[C:6](=[O:13])[N:5]([C:14]5[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=5)[N:4]([CH2:3][C:2]([OH:1])([CH3:20])[CH3:21])[C:8]=4[CH3:9])=[O:12])=[CH:67][CH:68]=3)[CH:53]=2)[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 533934301-(2-Hydroxy-2-methylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydropyrazole-4-carboxylic AcidHCID 667793254-[(2-Phenylfuro[3,2-b]pyridin-7-yl)oxy]aniline

Product 1

HCID 667797701-(2-Hydroxy-2-methyl-propyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid [4-(2-phenyl-furo[3,2-b]pyridin-7-yloxy)-phenyl]-amideYield 15%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a 10 mL sealed tube with stirbar was added 1-(2-hydroxy-2-methyl-propyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (57.62 mg; 0.20 mmol; 1.20 eq.), and bis(2-oxo-3-oxazolidinyl)phosphinic chloride (63.15 mg; 0.25 mmol; 1.50 eq.). The tube was sealed and flushed with N2. To this mixture was added dioxane (3.00 ml) and N,N-diisopropylethylamine (0.14 ml; 0.83 mmol; 4.00 eq.) and the mixture was stirred at room temperature for 1 h. To the reaction mixture was then added 4-[(2-phenylfuro[3,2-b]pyridin-7-yl)oxy]aniline (50.00 mg; 0.17 mmol; 1.00 eq.) and stirred at room temperature overnight. The reaction mixture was concentrated on a rotary evaporator. The crude mixture was purified by Biotage chromatography (50% EtOAc/hex 10 column vol.; 50-100% 10 column vol.) to afford a beige solid (14 mg, 15%). (HPLC (method F): 88%, RT: 6.27 min); 1H NMR (400 MHz, DMSO-d6) δ [ppm] 10.84 (s, 1H), 8.35 (d, J=5.6, 1H), 7.98-7.90 (m, 2H), 7.73 (d, J=9.0, 2H), 7.70 (s, 1H), 7.60-7.50 (m, 4H), 7.49-7.43 (m, 2H), 7.35 (d, J=7.4, 2H), 7.30 (d, J=9.0, 2H), 6.71 (d, J=5.5, 1H), 4.85 (s, 1H), 3.86 (s, 2H), 2.80 (s, 3H), 0.97 (s, 6H); MS (m/z) 575 [M+H]+, RT: 3.7 min.

Workup

  1. customTo a 10 mL sealed tube with stirbar
  2. customThe tube was sealed
  3. customflushed with N2
  4. concentrationThe reaction mixture was concentrated on a rotary evaporator
  5. customThe crude mixture was purified by Biotage chromatography (50% EtOAc/hex 10 column vol.; 50-100% 10 column vol.)

Sources & evidence

ORD record
ord-1b4ab0926d6b43a0a10964150633b81d
Source dataset
uspto-grants-2015_04
Patent number
US09006440B2

Reaction notes

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