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

HRID 407761Notes

Reaction equation

HRID 407761 reaction equation
C([O:4][CH2:5][C:6]1[C:7]([N:28]2[N:37]=[CH:36][C:35]3[C:30](=[C:31]([F:42])[CH:32]=[C:33]([C:38]([CH3:41])([CH3:40])[CH3:39])[CH:34]=3)[C:29]2=[O:43])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:23]=[CH:22][N:21]([CH2:24][CH3:25])[N:20]=2)[C:15](=[O:26])[N:14]([CH3:27])[CH:13]=1)(=O)C.C1COCC1.O>ClCCl>[C:38]([C:33]1[CH:34]=[C:35]2[C:30](=[C:31]([F:42])[CH:32]=1)[C:29](=[O:43])[N:28]([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]=[CH:22][N:21]([CH2:24][CH3:25])[N:20]=4)[C:15](=[O:26])[N:14]([CH3:27])[CH:13]=3)[CH:10]=[CH:9][N:8]=1)[N:37]=[CH:36]2)([CH3:40])([CH3:39])[CH3:41]

Participants

5

Reactant 3

HCID 962WaterHCID 8028TetrahydrofuranHCID 86684027(2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(5-(1-ethyl-1H-pyrazol-3-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl acetate

Product 1

HCID 866840286-Tert-butyl-2-[4-[5-[(1-ethylpyrazol-3-yl)amino]-1-methyl-6-oxo-3-pyridyl]-3-(hydroxymethyl)-2-pyridyl]-8-fluoro-phthalazin-1-oneYield 19%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Into a 1 dram vial was added 142d (1 equiv) in a 4:1 mixture of THF and water (1 mL) Lithium hydroxide (1.5 equiv) was then added to the mixture and the reaction was stirred at room temperature for 16 hours. The reaction was then diluted with dichloromethane (3 mL) and washed with water (2×3 mL). The organic layer was collected, dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude material was purified by reverse-phase chromatography to give 142 (7.6 mg, 19% yield). 1H NMR (400 MHz, DMSO-d6) δ 8.55 (s, 1H), 8.52 (d, J=2.5 Hz, 1H), 8.16 (s, 1H), 8.06 (d, J=2.5 Hz, 1H), 7.89 (m, 1H), 7.75 (dd, J=13.1, 1.9 Hz, 1H), 7.53 (d, J=2.2 Hz, 1H), 7.51 (d, J=12.6 Hz, 1H), 7.40 (d, J=2.1 Hz, 1H), 6.07 (s, 1H), 4.46 (br s 1H), 4.00 (q, J=7.2 Hz, 2H), 3.60 (s, 3H), 3.17 (s, 2H), 1.39 (s, 9H), 1.34 (t, J=7.2 Hz, 3H). ES-MS m/z 544.3 [M+1].

Workup

  1. additionwas then added to the mixture
  2. washwashed with water (2×3 mL)
  3. customThe organic layer was collected
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by reverse-phase chromatography

Sources & evidence

ORD record
ord-384101861a27492bbfbbe987fbb702c0
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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