Dimethylamine → N'-[4-(1-ethyl-4-{2-[3-(hydroxymethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)phenyl]-N,N-dimethylurea

HRID 28911ノート

反応式

HRID 28911 の反応式
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]3[CH:18]=[CH:17][N:16]=[C:15]4[NH:19][C:20]([C:22]5[CH:23]=[C:24]([CH2:28][OH:29])[CH:25]=[CH:26][CH:27]=5)=[CH:21][C:14]=34)=[CH:11][N:10]([CH2:30][CH3:31])[N:9]=2)=[CH:4][CH:3]=1.[CH3:32][N:33]1[CH2:38]COC[CH2:34]1.CNC.C1C[O:45]CC1>>[CH2:30]([N:10]1[CH:11]=[C:12]([C:13]2[CH:18]=[CH:17][N:16]=[C:15]3[NH:19][C:20]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][OH:29])[CH:23]=4)=[CH:21][C:14]=23)[C:8]([C:5]2[CH:4]=[CH:3][C:2]([NH:1][C:38](=[O:45])[N:33]([CH3:32])[CH3:34])=[CH:7][CH:6]=2)=[N:9]1)[CH3:31]

参加物

5

反応物 4

HCID 674DimethylamineHCID 79724-MethylmorpholineHCID 8028Tetrahydrofuran2 回HCID 58980005(3-{4-[3-(4-aminophenyl)-1-ethyl-1H-pyrazol-4-yl]-1H-pyrrolo[2,3-b]pyridin-2-yl}phenyl)methanol

生成物 1

HCID 58980000N'-[4-(1-ethyl-4-{2-[3-(hydroxymethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)phenyl]-N,N-dimethylurea

実験手順

To a vigorously stirred solution of (3-{4-[3-(4-aminophenyl)-1-ethyl-1H-pyrazol-4-yl]-1H-pyrrolo[2,3-b]pyridin-2-yl}phenyl)methanol (16.13 g, 39.4 mMol) in THF (400 mL) was added NMM (4.5 mL, 40.9 mMol) followed by p-nitrophenylchloroformate (7.9 g, 39.2 mMol). (The reaction quickly became a fine suspension.) After stirring for 1 h at RT, a solution of 2.0 M dimethylamine in THF (200 mL, 400 mMol) was added. The reaction was stirred an additional 1 h at RT then concentrated to dryness under vacuum. The residue which remained was triturated with a cold solution of aq. 1 N NaOH (100 mL) in ice water (200 mL), filtered, washed with cold water (100 mL), and dried under vacuum. Purification by flash chromatography on silica gel (2 to 10% MeOH/CHCl3) gave the title product (16.67 g, 85% pure containing ˜15% starting aniline by LCMS, 75%) as a yellow solid: MS (ES) m/e 481.4 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ 12.14 (d, J=1.8 Hz, 1H), 8.31 (s, 1H), 8.26 (s, 1H), 8.07 (d, J=4.8 Hz, 1H), 7.83 (s, 1H), 7.77 (d, J=7.8 Hz, 1H), 7.42 (d, J=8.6 Hz, 2H), 7.41 (m, 1H), 7.29 (m, 1H), 7.28 (d, J=8.6 Hz, 2H), 6.79 (s, 1H), 6.78 (d, J=4.8 Hz, 1H), 5.26 (t, J=5.7 Hz, 1H), 4.56 (d, J=5.6 Hz, 2H), 4.27 (q, J=7.3 Hz, 2H), 2.91 (s, 6H), 1.51 (t, J=7.3 Hz, 3H).

後処理

  1. custom(The reaction
  2. stirringThe reaction was stirred an additional 1 h at RT
  3. concentrationthen concentrated to dryness under vacuum
  4. customThe residue which remained was triturated with a cold solution of aq. 1 N NaOH (100 mL) in ice water (200 mL)
  5. filtrationfiltered
  6. washwashed with cold water (100 mL)
  7. customdried under vacuum
  8. customPurification by flash chromatography on silica gel (2 to 10% MeOH/CHCl3)

出典と根拠

ORDレコード
ord-6828b331e4704d89b630483d8e3b32d5
出典データセット
uspto-grants-2008_09
特許番号
US07419988B2

反応ノート

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