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 1727742Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1727742
[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]

Komponenten

5

Edukt 4

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

Produkt 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

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-7f989928129f4accb58528f5748bf46e
Quelldatensatz
uspto-grants-2009_02
Patentnummer
US07495102B2

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