Dimethylamine → Gsk-1070916

HRID 1821224Notes

Reaction equation

HRID 1821224 reaction equation
[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](CO)[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.[CH3:39][NH:40][CH3:41].C1[CH2:46][O:45]CC1>>[CH3:32][N:33]([CH2:38][C:24]1[CH:23]=[C:22]([C:20]2[NH:19][C:15]3=[N:16][CH:17]=[CH:18][C:13]([C:12]4[C:8]([C:5]5[CH:6]=[CH:7][C:2]([NH:1][C:46](=[O:45])[N:40]([CH3:41])[CH3:39])=[CH:3][CH:4]=5)=[N:9][N:10]([CH2:30][CH3:31])[CH:11]=4)=[C:14]3[CH:21]=2)[CH:27]=[CH:26][CH:25]=1)[CH3:34]

Participants

5

Reactant 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

Product 1

HCID 46885626Gsk-1070916

Procedure

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) 12.14 (d, J=1.8 Hz, 1 H), 8.31 (s, 1 H), 8.26 (s, 1 H), 8.07 (d, J=4.8 Hz, 1 H), 7.83 (s, 1 H), 7.77 (d, J=7.8 Hz, 1 H), 7.42 (d, J=8.6 Hz, 2 H), 7.41 (m, 1 H), 7.29 (m, 1 H), 7.28 (d, J=8.6 Hz, 2 H), 6.79 (s, 1 H), 6.78 (d, J=4.8 Hz, 1 H), 5.26 (t, J=5.7 Hz, 1 H), 4.56 (d, J=5.6 Hz, 2 H), 4.27 (q, J=7.3 Hz, 2 H), 2.91 (s, 6 H), 1.51 (t, J=7.3 Hz, 3 H).

Workup

  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)

Sources & evidence

ORD record
ord-bdd4d8af3c1a4740a0833bb7e81ccb53
Source dataset
uspto-grants-2009_10
Patent number
US07605266B2

Reaction notes

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