Triethylamine → HCID 57639703, compound

HRID 1897482Notes

Reaction equation

HRID 1897482 reaction equation
[F:1][C:2]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:3]=1[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[C:14](O)=[O:15])[N:10]([CH2:17][CH:18]([CH3:20])[CH3:19])[N:9]=[CH:8]2.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[NH2:49][C@@H:50]([CH2:55][CH2:56][N:57]([CH3:59])[CH3:58])[C:51]([O:53][CH3:54])=[O:52].C(N(CC)CC)C>ClC(Cl)C.ClCCl>[F:1][C:2]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:3]=1[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[C:14]([NH:49][C@@H:50]([CH2:55][CH2:56][N:57]([CH3:59])[CH3:58])[C:51]([O:53][CH3:54])=[O:52])=[O:15])[N:10]([CH2:17][CH:18]([CH3:20])[CH3:19])[N:9]=[CH:8]2

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 574187635-(2,4-Difluorophenoxy)-1-isobutyl-1H-indazole-6-carboxylic acidHCID 86594424HCID 86594424, compound

Product 1

HCID 57639703HCID 57639703, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Procedure

5-(2,4-Difluorophenoxy)-1-isobutyl-1H-indazole-6-carboxylic acid (17d; prepared according to Example 110) (0.396 g, 1.14 mmol) was stirred with HOBt (0.192 g, 1.26 mmol) and EDCI (0.241 g, 1.26 mmol) in dichloroethane (2 mL) for 10 minutes at room temperature. This mixture was then added to a suspension of (S)-methyl 2-amino-4-(dimethylamino)butanoate dihydrochloride (0.280 g, 1.20 mmol) and triethylamine (1 mL, 6.9 mmol) in dichloromethane (6 mL). The reaction mixture was stirred for 3 hours and then was concentrated under reduced pressure. The residue was diluted with chloroform (50 mL) and washed with 1N HCl (2×25 mL), saturated K2CO3 (2×50 mL), water (25 mL), brine (25 mL), and dried over MgSO4. The filtered solution was concentrated under reduced pressure to provide yellow oil. The oil was chromatographed eluting with 5% MeOH in dichloromethane to afford a viscous colorless oil that solidified upon drying under high vacuum (0.393 g, 71% yield). MS (ESI+) m/z 489 (M+1) detected; 1H NMR (400 mHz, CDCl3) δ 8.91 (d, 1H), 8.36 (s, 1H), 7.86 (s, 1H), 7.16 (m, 1H), 7.03 (m, 1H), 7.00 (s, 1H), 6.93 (m, 1H), 4.88 (m, 1H), 4.21 (d, 2H), 3.74 (s, 3H), 2.34 (m, 3H), 2.06 (s, 6H), 2.01 (m, 2H), 0.92 (d, 6H).

Workup

  1. concentrationwas concentrated under reduced pressure
  2. additionThe residue was diluted with chloroform (50 mL)
  3. washwashed with 1N HCl (2×25 mL), saturated K2CO3 (2×50 mL), water (25 mL), brine (25 mL)
  4. dry with materialdried over MgSO4
  5. concentrationThe filtered solution was concentrated under reduced pressure
  6. customto provide yellow oil
  7. customThe oil was chromatographed
  8. washeluting with 5% MeOH in dichloromethane
  9. customto afford a viscous colorless oil that
  10. customupon drying under high vacuum (0.393 g, 71% yield)

Sources & evidence

ORD record
ord-36b380e1b189497392071aab3dd93f6e
Source dataset
uspto-grants-2013_08
Patent number
US08518983B2

Reaction notes

Loading…