Isopropanol → 6-Tert-butyl-2-[4-[5-[(1-ethyl-5-methyl-pyrazol-3-yl)amino]-1-methyl-6-oxo-3-pyridyl]-3-(hydroxymethyl)-2-pyridyl]-8-fluoro-phthalazin-1-one

HRID 407665Notes

Reaction equation

HRID 407665 reaction equation
C([O:4][CH2:5][C:6]1[C:7]([N:29]2[N:38]=[CH:37][C:36]3[C:31](=[C:32]([F:43])[CH:33]=[C:34]([C:39]([CH3:42])([CH3:41])[CH3:40])[CH:35]=3)[C:30]2=[O:44])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:23]=[C:22]([CH3:24])[N:21]([CH2:25][CH3:26])[N:20]=2)[C:15](=[O:27])[N:14]([CH3:28])[CH:13]=1)(=O)C.[OH-].[Li+].C1COCC1.C(O)(C)C>O>[C:39]([C:34]1[CH:35]=[C:36]2[C:31](=[C:32]([F:43])[CH:33]=1)[C:30](=[O:44])[N:29]([C:7]1[C:6]([CH2:5][OH:4])=[C:11]([C:12]3[CH:17]=[C:16]([NH:18][C:19]4[CH:23]=[C:22]([CH3:24])[N:21]([CH2:25][CH3:26])[N:20]=4)[C:15](=[O:27])[N:14]([CH3:28])[CH:13]=3)[CH:10]=[CH:9][N:8]=1)[N:38]=[CH:37]2)([CH3:41])([CH3:40])[CH3:42]

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 86683949(2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(5-(1-ethyl-5-methyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl Acetate

Product 1

HCID 866839506-Tert-butyl-2-[4-[5-[(1-ethyl-5-methyl-pyrazol-3-yl)amino]-1-methyl-6-oxo-3-pyridyl]-3-(hydroxymethyl)-2-pyridyl]-8-fluoro-phthalazin-1-oneYield 27.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 118c (80 mg, 0.13 mmol), lithium hydroxide (13 mg, 0.53 mmol), THF (6 mL), i-propanol (4 mL) and water (2 mL) was stirred at room temperature for 0.5 h. The mixture was concentrated under reduced pressure and diluted with water (5 mL). It was then extracted with dichloromethane (2×10 mL). The combined dichloromethane extract was concentrated under reduced pressure and the residue was purified with reverse-phase prep-HPLC to afford 118 (20 mg, 26%) as a white solid. MS-ESI: [M+H]+ 558.3. 1H NMR (500 MHz, DMSO-d6) δ 8.56 (d, J=5.0 Hz, 1H), 8.53 (d, J=2.5 Hz, 1H), 8.10 (s, 1H), 8.05 (d, J=2.5 Hz, 1H), 7.90 (d, J=2.0 Hz, 1H), 7.79-7.76 (m, 1H), 7.50 (d, J=5.0 Hz, 1H), 7.40 (d, J=2.5 Hz, 1H), 5.88 (s, 1H), 4.92 (t, J=5.0 Hz 1H), 4.46-4.45 (m, 2H), 3.91 (q, J=7.5 Hz, 2H), 3.59 (s, 3H), 2.19 (s, 3H), 1.40 (s, 9H), 1.27 (t, J=7.0 Hz, 3H).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. additiondiluted with water (5 mL)
  3. extractionIt was then extracted with dichloromethane (2×10 mL)
  4. extractionThe combined dichloromethane extract
  5. concentrationwas concentrated under reduced pressure
  6. customthe residue was purified with reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-234435d43d1a4b07bda9dcb9712fa99b
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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