Triethylamine → (3-(3-Amino-2,6-difluorobenzoyl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-1-yl)(2,6-dichlorophenyl)methanone

HRID 1747254Notes

Reaction equation

HRID 1747254 reaction equation
[NH2:1][C:2]1[C:3]([F:21])=[C:4]([C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([Br:20])[CH:18]=3)[NH:13][CH:12]=2)=[O:10])[C:5]([F:8])=[CH:6][CH:7]=1.C(N(CC)CC)C.[Cl:29][C:30]1[CH:38]=[CH:37][CH:36]=[C:35]([Cl:39])[C:31]=1[C:32](Cl)=[O:33]>CN(C)C1C=CN=CC=1.CC1CCCO1>[NH2:1][C:2]1[C:3]([F:21])=[C:4]([C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([Br:20])[CH:18]=3)[N:13]([C:32](=[O:33])[C:31]3[C:30]([Cl:29])=[CH:38][CH:37]=[CH:36][C:35]=3[Cl:39])[CH:12]=2)=[O:10])[C:5]([F:8])=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 783922,6-Dichlorobenzoyl chlorideHCID 58368727(3-Amino-2,6-difluorophenyl)(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)methanone2×

Product 1

HCID 72549401(3-(3-Amino-2,6-difluorobenzoyl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-1-yl)(2,6-dichlorophenyl)methanoneYield 92.93%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 73012-MethyltetrahydrofuranSolvent

Conditions

Temperature
9.300000190734863 °C

Procedure

Compound 4 (2.5 kg, 7.114 mol) obtained from Example 2 was added into a 50-liter flask and cooled to 9.3° C. To compound 4 in the 50-liter flask was added triethylamine (0.864 kg, 8.537 mol), followed by 4-dimethylaminopyridine (DMAP) (0.087 kg, 0.7114 mol) and 2,6-dichlorobenzoyl chloride (1.34 kg, 6.40 mol) in 2-methyl-THF (25 L) over a period of 2 hrs. The reaction was quenched with methanol (0.30 L at room temperature and added an aqueous NaCl solution (12.5 L, 15%) and celite (0.5 kg). The mixture was stirred and filtered through celite. The filtrate was concentrated and added 5 volumes of heptanes. The resulting solution was stirred for about 1 hr and dried with sodium sulfate (1 kg) and filtered. Compound 5 was isolated by removing the solvents under vacuum (3.47 kg, 92.93% yield). MS (ESI): M+H+=524, 525.8, 527.8. 1H NMR (DMSO-d6, δ ppm): 5.36 (2H, s), 7.01 (2H, m), 7.68 (3H, s), 8.34 (1H, brs), 8.61 (1H, brs), 8.72 (1H, d J=2.3 Hz).

Workup

  1. customThe reaction was quenched with methanol (0.30 L at room temperature
  2. additionadded an aqueous NaCl solution (12.5 L, 15%) and celite (0.5 kg)
  3. filtrationfiltered through celite
  4. concentrationThe filtrate was concentrated
  5. additionadded 5 volumes of heptanes
  6. stirringThe resulting solution was stirred for about 1 hr
  7. dry with materialdried with sodium sulfate (1 kg)
  8. filtrationfiltered

Sources & evidence

ORD record
ord-a256fed6bb8b4bf2ac3daee609c08ae4
Source dataset
uspto-grants-2015_10
Patent number
US09150570B2

Reaction notes

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