3-Methylpentanoic acid → 3-methyl-pentanoic acid {1-benzenesulfonyl-4-[1-(2-cyano-ethyl)-piperidin-4-ylamino]-1H-pyrrolo[2,3-b]pyridin-5-yl}-amide

HRID 1257610ノート

反応式

HRID 1257610 の反応式
[CH3:1][CH:2]([CH2:7][CH3:8])[CH2:3][C:4]([OH:6])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[NH2:42][C:43]1[C:44]([NH:61][CH:62]2[CH2:67][CH2:66][N:65]([CH2:68][CH2:69][C:70]#[N:71])[CH2:64][CH2:63]2)=[C:45]2[CH:51]=[CH:50][N:49]([S:52]([C:55]3[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=3)(=[O:54])=[O:53])[C:46]2=[N:47][CH:48]=1>CN(C=O)C>[C:55]1([S:52]([N:49]2[C:46]3=[N:47][CH:48]=[C:43]([NH:42][C:4](=[O:6])[CH2:3][CH:2]([CH3:1])[CH2:7][CH3:8])[C:44]([NH:61][CH:62]4[CH2:63][CH2:64][N:65]([CH2:68][CH2:69][C:70]#[N:71])[CH2:66][CH2:67]4)=[C:45]3[CH:51]=[CH:50]2)(=[O:53])=[O:54])[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1

参加物

6

反応物 4

HCID 77553-Methylpentanoic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 673456183-[4-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidin-1-yl]-propionitrile

生成物 1

HCID 673443913-methyl-pentanoic acid {1-benzenesulfonyl-4-[1-(2-cyano-ethyl)-piperidin-4-ylamino]-1H-pyrrolo[2,3-b]pyridin-5-yl}-amide収率 110%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
25 °C

実験手順

Racemic 3-methylpentanoic acid (0.180 ml, 1.4 mmol), HATU (0.53 g, 1.4 mmol), and diisopropylethylamine (0.46 ml, 2.7 mmol), were added sequentially to a solution of 3-[4-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidin-1-yl]-propionitrile (0.54 g, 1.3 mmol, prepared as described in Example 118) in DMF (20 ml) at 25° C. The reaction mixture was stirred for 4 h at 25° C., then was concentrated under reduced pressure. The residue was partitioned between half-saturated NaHCO3 (100 ml) and EtOAc (2×200 ml). The organic layers were dried over MgSO4, filtered, and the filtrate was concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel (gradient: 0 to 8% CH3OH in CH2Cl2) afforded 3-methyl-pentanoic acid {1-benzenesulfonyl-4-[1-(2-cyano-ethyl)-piperidin-4-ylamino]-1H-pyrrolo[2,3-b]pyridin-5-yl}-amide (0.706 g, 110%) as an off-white solid. LCMS (Method G, ESI): RT=0.73 min, m+H=523.4. This material was used in the next step below without further characterization.

後処理

  1. concentrationwas concentrated under reduced pressure
  2. customThe residue was partitioned between half-saturated NaHCO3 (100 ml) and EtOAc (2×200 ml)
  3. dry with materialThe organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customPurification of the residue by column chromatography on silica gel (gradient: 0 to 8% CH3OH in CH2Cl2)

出典と根拠

ORDレコード
ord-4147295757a64182a2c54c9184e3e660
出典データセット
uspto-grants-2013_06
特許番号
US08461328B2

反応ノート

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