1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 2-(4-iodo-6-oxo-6H-pyridazin-1-yl)-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide

HRID 2381403Notes

Reaction equation

HRID 2381403 reaction equation
[CH3:1][C:2]1([CH3:14])[O:6][C@H:5]([CH2:7][N:8]2[CH:12]=[CH:11][C:10]([NH2:13])=[N:9]2)[CH2:4][O:3]1.[I:15][C:16]1[CH:17]=[N:18][N:19]([CH:23]([CH2:27][CH:28]([CH3:30])[CH3:29])[C:24](O)=[O:25])[C:20](=[O:22])[CH:21]=1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[CH3:1][C:2]1([CH3:14])[O:6][C@H:5]([CH2:7][N:8]2[CH:12]=[CH:11][C:10]([NH:13][C:24](=[O:25])[CH:23]([N:19]3[C:20](=[O:22])[CH:21]=[C:16]([I:15])[CH:17]=[N:18]3)[CH2:27][CH:28]([CH3:30])[CH3:29])=[N:9]2)[CH2:4][O:3]1

Participants

7

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 579193122-(4-iodo-6-oxo-6H-pyridazin-1-yl)-4-methyl-pentanoic acid2×HCID 59344941(R)-1-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-amine2×

Product 1

HCID 579192872-(4-iodo-6-oxo-6H-pyridazin-1-yl)-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amideYield 51.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-ylamine (Intermediate 4, 708.7 mg, 3.59 mmol) in N,N-dimethylformamide was added to 2-(4-iodo-6-oxo-6H-pyridazin-1-yl)-4-methyl-pentanoic acid (Intermediate 86, 1.42 g, 4.23 mmol). At this point, the reaction was treated with 4-dimethylaminopyridine (21.9 mg, 0.18 mmol) followed by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (823.7 mg, 4.31 mmol). The resulting reaction was stirred at 25° C. overnight. The reaction was then diluted with ethyl acetate (200 mL), was washed with water (200 mL) and a saturated aqueous sodium chloride solution (200 mL), filtered, and concentrated in vacuo onto silica gel. Chromatography (ISCO Combiflash, 10-60% ethyl acetate/hexanes) afforded 2-(4-iodo-6-oxo-6H-pyridazin-1-yl)-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide as a white/yellow solid (950 mg, 51%); ES+-HRMS m/e calcd for C19H26N5O4I [M+Na+] 538.0921, found 538.0921. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.83 (d, J=5.7 Hz, 3H), 0.85 (d, J=5.7 Hz, 3H), 1.23 (s, 3H), 1.29 (s, 3H), 1.35 (br. s., 1H), 1.76 (ddd, J=13.3, 9.4, 4.2 Hz, 1H), 2.03-2.21 (m, 1H), 3.71 (dd, J=8.4, 6.0 Hz, 1H), 3.98 (dd, J=8.4, 6.5 Hz, 1H), 4.03-4.18 (m, 2H), 4.33 (quin, J=6.0 Hz, 1H), 5.47 (dd, J=11.0, 4.1 Hz, 1H), 6.36 (d, J=2.1 Hz, 1H), 7.58 (d, J=1.8 Hz, 1H), 7.59 (d, J=2.1 Hz, 1H), 8.23 (d, J=1.8 Hz, 1H), 10.82 (s, 1H).

Workup

  1. customThe resulting reaction
  2. washwas washed with water (200 mL)
  3. filtrationa saturated aqueous sodium chloride solution (200 mL), filtered
  4. concentrationconcentrated in vacuo onto silica gel

Sources & evidence

ORD record
ord-8e981d79a0f649f8962ce43a32d324bb
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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