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 402948ノート

反応式

HRID 402948 の反応式
[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]

参加物

5

反応物 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

生成物 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-one収率 16%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-ef9afe9e5ff048569748c015d4ae1910
出典データセット
uspto-grants-2014_06
特許番号
US08742098B2

反応ノート

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