Methanol → HCID 44464040, compound

HRID 2381479Notes

Reaction equation

HRID 2381479 reaction equation
C[O:2][C:3](=[O:39])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:38])[CH:12]([N:19]2[C:24](=[O:25])[CH:23]=[C:22]([O:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[CH:33]3[CH2:37][CH2:36][CH2:35][CH2:34]3)[CH:21]=[N:20]2)[CH2:13][CH:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)=[N:6][CH:5]=1.[OH-].[Li+].CO>O1CCCC1>[CH:14]1([CH2:13][CH:12]([N:19]2[C:24](=[O:25])[CH:23]=[C:22]([O:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[CH:33]3[CH2:34][CH2:35][CH2:36][CH2:37]3)[CH:21]=[N:20]2)[C:11]([NH:10][C:7]2[CH:8]=[CH:9][C:4]([C:3]([OH:39])=[O:2])=[CH:5][N:6]=2)=[O:38])[CH2:18][CH2:17][CH2:16][CH2:15]1

Participants

5

Reactant 3

HCID 887MethanolHCID 3939Lithium HydroxideHCID 57919228HCID 57919228, compound

Product 1

HCID 44464040HCID 44464040, compoundYield 30.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 6-{3-cyclopentyl-2-[4-(2-cyclopentyl-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionylamino}-nicotinic acid methyl ester (Example 66, 130 mg, 0.24 mmol) in tetrahydrofuran (5.0 mL) at 25° C. was treated with a 0.5N aqueous lithium hydroxide solution (1.0 mL) and methanol (1.0 mL). The resulting solution was stirred at 25° C. for 5 h. After this time, the solution was concentrated in vacuo. The residue was treated with a 1N aqueous hydrochloric acid solution (0.6 mL). The mixture was extracted with ethyl acetate. The organics were then washed with a saturated aqueous sodium chloride solution and then concentrated in vacuo. The resulting solids were triturated with hexanes and diethyl ether. The resulting solids were collected by filtration and dried in vacuo to afford 6-{3-cyclopentyl-2-[4-(2-cyclopentyl-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionylamino}-nicotinic acid (38 mg) as a solid; ES+-HRMS m/e calcd for C29H32N4O5 [M+H+] 517.2446 found 517.2443. 1H-NMR (300 MHz, DMSO-d6) δ ppm 1.03-2.05 (m, 18H), 2.31 (m, 1H), 3.04 (m, 1H), 5.57 (dd, J=4.2, J=10.6 Hz, 1H), 5.61 (d, J=2.7 Hz, 1H), 7.20 (m, 1H), 7.27-7.38 (m, 2H), 7.49 (m, 1H), 8.08 (d, Jo=8.8 Hz, 1H), 8.20 (d, J=2.7 Hz, 1H), 8.24 (dd, Jo=8.8 Hz, Jm=2.2 Hz, 1H), 8.84 (d, Jm=2.2 Hz, 1H), 11.33 (s, 1H), 13.18 (br.s., 1H).

Workup

  1. concentrationAfter this time, the solution was concentrated in vacuo
  2. additionThe residue was treated with a 1N aqueous hydrochloric acid solution (0.6 mL)
  3. extractionThe mixture was extracted with ethyl acetate
  4. washThe organics were then washed with a saturated aqueous sodium chloride solution
  5. concentrationconcentrated in vacuo
  6. customThe resulting solids were triturated with hexanes and diethyl ether
  7. filtrationThe resulting solids were collected by filtration
  8. customdried in vacuo

Sources & evidence

ORD record
ord-f9c5b4b38c444caab8886f8805fe4782
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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