Diisopropylethylamine → 3-(4-Cyclopropyl-2-fluoro-phenylamino)1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (2-vinyloxy-ethoxy)-amide

HRID 2264992ノート

反応式

HRID 2264992 の反応式
[CH:1]1([C:4]2[CH:9]=[CH:8][C:7]([NH:10][C:11]3[C:15]4[CH:16]=[N:17][CH:18]=[CH:19][C:14]=4[N:13]([CH3:20])[C:12]=3[C:21]([OH:23])=O)=[C:6]([F:24])[CH:5]=2)[CH2:3][CH2:2]1.[CH:25]([O:27][CH2:28][CH2:29][O:30][NH2:31])=[CH2:26].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C1COCC1>[CH:25]([O:27][CH2:28][CH2:29][O:30][NH:31][C:21]([C:12]1[N:13]([CH3:20])[C:14]2[CH:19]=[CH:18][N:17]=[CH:16][C:15]=2[C:11]=1[NH:10][C:7]1[CH:8]=[CH:9][C:4]([CH:1]2[CH2:3][CH2:2]2)=[CH:5][C:6]=1[F:24])=[O:23])=[CH2:26]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 595964403-(4-Cyclopropyl-2-fluoro-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid

生成物 1

HCID 595965283-(4-Cyclopropyl-2-fluoro-phenylamino)1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (2-vinyloxy-ethoxy)-amide収率 33.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A suspension of 3-(4-cyclopropyl-2-fluoro-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (88 mg, 0.25 mmol), O-(2-vinyloxy-ethyl)-hydroxylamine (028 mg, 0.28 mmol), HATU (114 mg, 0.30 mmol) and DIPEA (0.052 ml, 0.30 mmol) in THF (3 ml) was stirred at ambient temperature for 18 hours. On completion of the reaction, the mixture was concentrated in vacuo then re-dissolved in DCM. The solution was washed with saturated aqueous NaHCO3 and brine, dried over magnesium sulphate then concentrated in vacuo. The resultant residue was purified by flash chromatography (Si-PPC, DCM:MeOH, gradient 99:1 to 90:10) to give a yellow solid (34 mg, 33%). LCMS (method B): RT=2.46 min, M+H+=411. 1H NMR (CDCl3): 8.58 (1H, s), 8.41-8.36 (1H, m), 7.30 (1H, d, J=6.08 Hz), 7.26 (1H, d, J=1.99 Hz), 6.87 (1H, dd, J=8.33, 2.02 Hz), 6.47 (1H, dd, J=8.34, 3.82 Hz), 5.85 (1H, s), 4.11 (3H, s), 3.97-3.90 (2H, m), 3.71 (2H, dd, J=5.23, 3.41 Hz), 2.78 (1H, m), 1.22-1.13 (6H, m).

後処理

  1. customOn completion of the reaction
  2. concentrationthe mixture was concentrated in vacuo
  3. dissolutionthen re-dissolved in DCM
  4. washThe solution was washed with saturated aqueous NaHCO3 and brine
  5. dry with materialdried over magnesium sulphate
  6. concentrationthen concentrated in vacuo
  7. customThe resultant residue was purified by flash chromatography (Si-PPC, DCM:MeOH, gradient 99:1 to 90:10)

出典と根拠

ORDレコード
ord-c1a1d7dbc0754ad5a07a2dd7a1e09937
出典データセット
uspto-grants-2010_12
特許番号
US07855216B2

反応ノート

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