Water → 6-tert-Butyl-8-fluoro-2-(2-hydroxymethyl-3-{8-[4-(morpholine-4-carbonyl)-phenylamino]-imidazo[1,2-a]pyridin-6-yl}-phenyl)-2H-phthalazin-1-one

HRID 402948Notes

Reaction equation

HRID 402948 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]3[CH:29]=[C:30]([NH:37][C:38]4[CH:43]=[CH:42][C:41]([C:44]([N:46]5[CH2:51][CH2:50][O:49][CH2:48][CH2:47]5)=[O:45])=[CH:40][CH:39]=4)[C:31]4[N:32]([CH:34]=[CH:35][N:36]=4)[CH:33]=3)[C:18]=1[CH2:19][O:20]C(=O)C)[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].O>CO>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]3[CH:29]=[C:30]([NH:37][C:38]4[CH:39]=[CH:40][C:41]([C:44]([N:46]5[CH2:47][CH2:48][O:49][CH2:50][CH2:51]5)=[O:45])=[CH:42][CH:43]=4)[C:31]4[N:32]([CH:34]=[CH:35][N:36]=4)[CH:33]=3)[C:18]=1[CH2:19][OH:20])[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 962WaterHCID 11430Potassium CarbonateHCID 86686845acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-{8-[4-(morpholine-4-carbonyl)-phenylamino]-imidazo[1,2-a]pyridin-6-yl}-benzyl ester

Product 1

HCID 866868466-tert-Butyl-8-fluoro-2-(2-hydroxymethyl-3-{8-[4-(morpholine-4-carbonyl)-phenylamino]-imidazo[1,2-a]pyridin-6-yl}-phenyl)-2H-phthalazin-1-oneYield 16%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-{8-[4-(morpholine-4-carbonyl)-phenylamino]-imidazo[1,2-a]pyridin-6-yl}-benzyl ester (200 mg, 0.29 mmol) was dissolved in methanol (10 ml). To this solution was added K2CO3 (80 mg, 0.58 mmol) and the mixture was stirred at room temperature for 2 hours. After the completion of the reaction, the mixture was poured into water (10 ml), extracted by DCM (100 ml). The organic extracts were washed with saturated aqueous solution of sodium chloride (100 ml), dried over sodium sulfate and concentrated. The residue was purified by silica gel column (petroleum ether:ethyl acetate 1:3) to afford the desired product as a yellow solid (30 mg, yield 16%). 1H NMR (300 MHz, CDCl3): δ 8.37 (d, J=2.7 Hz, 1H), 8.04 (d, J=1.3 Hz, 1H), 7.78 (s, 1H), 7.73 (d, J=1.7 Hz, 1H), 7.61 (d, J=1.7 Hz, 1H), 7.57 (d, J=1.6 Hz, 1H), 7.45 (dd, J=7.7, 5.7 Hz, 3H), 7.36 (dd, J=6.6, 2.7 Hz, 1H), 7.32 (s, 3H), 7.19 (d, J=1.4 Hz, 1H), 4.38 (s, 2H), 3.57 (s, 8H), 1.35 (s, 9H). LC-MS: 647[M+1]+, tR=1.407 min. HPLC: 97.75% at 214 nm, 98.27% at 254 nm, tR=3.633 min.

Workup

  1. customAfter the completion of the reaction
  2. extractionextracted by DCM (100 ml)
  3. washThe organic extracts were washed with saturated aqueous solution of sodium chloride (100 ml)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column (petroleum ether:ethyl acetate 1:3)

Sources & evidence

ORD record
ord-ef9afe9e5ff048569748c015d4ae1910
Source dataset
uspto-grants-2014_06
Patent number
US08742098B2

Reaction notes

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