Diisopropylethylamine → 2-[4-(benzotriazol-1-yloxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclopentyl-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-propionamide

HRID 2381537Notes

Reaction equation

HRID 2381537 reaction equation
[CH:1]1([CH2:6][CH:7]([N:11]2[C:16](=[O:17])[CH:15]=[C:14](I)[CH:13]=[N:12]2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.[N:35]1([O:44][P+](N(C)C)(N(C)C)N(C)C)[C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=2[N:37]=[N:36]1.[CH3:55][C:56]1([CH3:68])[O:60][C@H:59]([CH2:61][N:62]2[CH:66]=[CH:65][C:64]([NH2:67])=[N:63]2)[CH2:58][O:57]1>CN(C)C=O.C(OCC)(=O)C>[N:35]1([O:44][C:14]2[CH:13]=[N:12][N:11]([CH:7]([CH2:6][CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)[C:8]([NH:67][C:64]3[CH:65]=[CH:66][N:62]([CH2:61][C@@H:59]4[CH2:58][O:57][C:56]([CH3:68])([CH3:55])[O:60]4)[N:63]=3)=[O:10])[C:16](=[O:17])[CH:15]=2)[C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=2[N:37]=[N:36]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 579193103-cyclopentyl-2-(4-iodo-6-oxo-6H-pyridazin-1-yl)-propionic acid2×HCID 59344941(R)-1-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-amine2×

Product 1

HCID 668932872-[4-(benzotriazol-1-yloxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclopentyl-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-propionamideYield 51%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 3-cyclopentyl-2-(4-iodo-6-oxo-6H-pyridazin-1-yl)-propionic acid (Intermediate 85, 1.44 g, 3.98 mmol) in N,N-dimethylformamide (18 mL, 0.22M) at 25° C. was treated with N,N-diisopropylethylamine (2.0 mL, 12.10 mmol), (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (2.64 g, 5.97 mmol) and 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-ylamine (Intermediate 4, 0.88 g, 4.46 mmol). The reaction was stirred at 25° C. over 3 nights. After this time, the reaction was diluted with ethyl acetate (150 mL) and was washed with a saturated aqueous ammonium chloride solution (150 mL), a saturated aqueous sodium bicarbonate solution (150 mL) and a saturated aqueous sodium chloride solution (150 mL), dried over magnesium sulfate, filtered, rinsed and concentrated in vacuo. Silica gel column chromatography (AnaLogix 80 g, 25-75% gradient ethyl acetate/hexanes) afforded 2-[4-(benzotriazol-1-yloxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclopentyl-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-propionamide (1.11 g, 51%) as an off-white solid as a mixture of diastereomers.

Workup

  1. washwas washed with a saturated aqueous ammonium chloride solution (150 mL)
  2. dry with materiala saturated aqueous sodium bicarbonate solution (150 mL) and a saturated aqueous sodium chloride solution (150 mL), dried over magnesium sulfate
  3. filtrationfiltered
  4. washrinsed
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-884b5a8038c5439293261f7daa99d63a
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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