Diisopropylethylamine → (2-{1-benzenesulfonyl-4-[1-(2-cyano-ethyl)-piperidin-4-ylamino]-1H-pyrrolo[2,3-b]pyridin-5-ylcarbamoyl}-ethyl)-carbamic acid 9H-fluoren-9-ylmethyl ester

HRID 1257605ノート

反応式

HRID 1257605 の反応式
[C:1]([NH:18][CH2:19][CH2:20][C:21](O)=[O:22])([O:3][CH2:4][CH:5]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]2[C:6]1=[CH:7][CH:8]=[CH:9][CH:10]=2)=[O:2].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.[NH2:57][C:58]1[C:59]([NH:76][CH:77]2[CH2:82][CH2:81][N:80]([CH2:83][CH2:84][C:85]#[N:86])[CH2:79][CH2:78]2)=[C:60]2[CH:66]=[CH:65][N:64]([S:67]([C:70]3[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=3)(=[O:69])=[O:68])[C:61]2=[N:62][CH:63]=1>CN(C=O)C>[CH:7]1[C:6]2[CH:5]([CH2:4][O:3][C:1](=[O:2])[NH:18][CH2:19][CH2:20][C:21](=[O:22])[NH:57][C:58]3[C:59]([NH:76][CH:77]4[CH2:78][CH2:79][N:80]([CH2:83][CH2:84][C:85]#[N:86])[CH2:81][CH2:82]4)=[C:60]4[CH:66]=[CH:65][N:64]([S:67]([C:70]5[CH:71]=[CH:72][CH:73]=[CH:74][CH:75]=5)(=[O:69])=[O:68])[C:61]4=[N:62][CH:63]=3)[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]=2[CH:10]=[CH:9][CH:8]=1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2724630N-Fluorenylmethoxycarbonyl-I2-alanineHCID 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 67345405(2-{1-benzenesulfonyl-4-[1-(2-cyano-ethyl)-piperidin-4-ylamino]-1H-pyrrolo[2,3-b]pyridin-5-ylcarbamoyl}-ethyl)-carbamic acid 9H-fluoren-9-ylmethyl ester収率 97%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
25 °C

実験手順

Fmoc-beta-Alanine (3.1 g, 9.90 mmol), HATU (3.8 g, 9.90 mmol), and diisopropylethylamine (2.1 ml, 12.0 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 (4.2 g, 9.90 mmol) in DMF (100 ml) at 25° C. The reaction mixture was stirred for 14 h at 25° C., then was concentrated under reduced pressure. The residue was partitioned between half-saturated NaHCO3 (200 ml) and EtOAc (2×200 ml). the combined organic layers were dried over Mg2SO4, filtered, and the filtrate was concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel (gradient: 0 to 7% CH3OH in CH2Cl2) afforded (2-{1-benzenesulfonyl-4-[1-(2-cyano-ethyl)-piperidin-4-ylamino]-1H-pyrrolo[2,3-b]pyridin-5-ylcarbamoyl}-ethyl)-carbamic acid 9H-fluoren-9-ylmethyl ester (6.89 g, 97%) as a white foam. LCMS (Method G, ESI): RT=0.85 min, m+H=718.5. 1H NMR (400 MHz, CDCl3, mixture of rotamers) δ 8.14 (t, J=10.3 Hz), 7.84 (s), 7.75 (dd, J=15.2, 7.5 Hz), 7.60-7.54 (m), 7.50 (d, J=4.1 Hz), 7.44 (t, J=7.8 Hz), 7.37 (t, J=7.4 Hz), 7.28 (t, J=5.8 Hz), 6.52 (t, J=4.7 Hz), 5.50 (d, J=11.4 Hz), 4.70 (s), 4.40 (s), 4.33 (d, J=7.1 Hz), 4.19 (t, J=6.6 Hz), 3.64 (td, J=13.3, 6.7 Hz), 3.51 (d, J=21.9 Hz), 3.39 (d, J=5.4 Hz), 2.80-2.47 (m), 2.35 (s), 2.30-2.07 (m), 1.93 (d, J=12.0 Hz), 1.51 (dt, J=13.5, 6.8 Hz).

後処理

  1. concentrationwas concentrated under reduced pressure
  2. customThe residue was partitioned between half-saturated NaHCO3 (200 ml) and EtOAc (2×200 ml)
  3. dry with materialthe combined organic layers were dried over Mg2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customPurification of the residue by column chromatography on silica gel (gradient: 0 to 7% CH3OH in CH2Cl2)

出典と根拠

ORDレコード
ord-5fc5ca75c2244d9098538f60488cf4ce
出典データセット
uspto-grants-2013_06
特許番号
US08461328B2

反応ノート

読み込み中…