Dimethylformamide → HCID 44182374, compound

HRID 1020957Notes

Reaction equation

HRID 1020957 reaction equation
Cl[CH2:2][C:3]([N:5]1[CH2:10][CH:9]=[C:8]([C:11]2S[C:13]([C:16]3[N:20]=[CH:19][N:18]([CH3:21])[N:17]=3)=[CH:14][CH:15]=2)[CH2:7][CH2:6]1)=[O:4].[CH:22]([O:25][C:26]1[N:31]=[CH:30][C:29]([C:32]2[C:40]3[C:35](=[CH:36][CH:37]=[C:38]([NH:41][C:42]([C:44]4(SC)[CH2:48][CH2:47][NH:46][CH2:45]4)=[O:43])[CH:39]=3)[NH:34][N:33]=2)=[CH:28][CH:27]=1)([CH3:24])[CH3:23].CCN([CH:57]([CH3:59])C)C(C)C.CN([CH:63]=[O:64])C>>[CH:22]([O:25][C:26]1[N:31]=[CH:30][C:29]([C:32]2[C:40]3[C:35](=[CH:36][CH:37]=[C:38]([NH:41][C:42]([C:44]4([O:64][CH3:63])[CH2:48][CH2:47][N:46]([CH2:2][C:3]([N:5]5[CH2:10][CH:9]=[C:8]([C:11]6[CH:59]=[CH:57][C:13]([C:16]7[N:20]=[CH:19][N:18]([CH3:21])[N:17]=7)=[CH:14][CH:15]=6)[CH2:7][CH2:6]5)=[O:4])[CH2:45]4)=[O:43])[CH:39]=3)[NH:34][N:33]=2)=[CH:28][CH:27]=1)([CH3:24])[CH3:23]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 58371903HCID 58371903, compoundHCID 67345075HCID 67345075, compound

Product 1

HCID 44182374HCID 44182374, compound

Procedure

A mixture of 2-chloro-1-{4-[5-(1-methyl-1H-[1,2,4]triazol-3-yl)-thiophen-2-yl]-3,6-dihydro-2H-pyridin-1-yl}-ethanone (8BW) (0.522 gm, 0.863 mmol), 3-Methylsulfanyl-pyrrolidine-3-carboxylic acid [3-(6-isopropoxy-pyridin-3-yl)-1H-indazol-5-yl]-amide (8BO) (0.463 gm, 0.95 mmol), and DIEA (0.9 ml, 5.2 mmol) in DMF (10 ml) was stirred at room temperature for overnight. DMF was removed under reduced pressure. The crude reaction mixture was precipitated in 30 ml ice cold water, filtered, dried, and purified by column chromatography using 10% MeOH/EtOAc to get desired product A24 as a yellow solid (70%). (LCMS M+1=698, ret. time=3.6 min.) 1H NMR (400 MHz, DMSO):8.67 (S, 1H), 8.64 (S, 1H), 8.36 (S, 1H), 8.15 (S, 1H), 7.64 (d, 1H, J=8.8 Hz), 7.52 (S, 1H), 7.49 (d, 1H J=5.2 Hz), 7.40 (d, 1H J=8.8 Hz), 7.02 (m, 1H), 6.18 (d, 1H, J=18.8 Hz), 5.08 (m, 1H), 4.41 (d, 2H, J=7.6 Hz), 4.34 (d, 1H, J=6.4 Hz)), 4.12 (S, 1H), 3.96 (s, 2H), 3.84 (S, 3H), 3.76 (S, 2H), 3.52 (S, 2H), 2.76 (S, 1H), 2.58 (d, 2H J=20.4 Hz), 2.13 (S, 3H), 1.94 (t, 2H J=2.8 Hz), 1.39 (d, 6H, J=4.8 Hz).

Workup

  1. customDMF was removed under reduced pressure
  2. customThe crude reaction mixture
  3. customwas precipitated in 30 ml ice cold water
  4. filtrationfiltered
  5. customdried
  6. custompurified by column chromatography

Sources & evidence

ORD record
ord-ac4ae5fc786f48fbbae747d67df155d0
Source dataset
uspto-grants-2014_05
Patent number
US08716483B2

Reaction notes

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