Diisopropylethylamine → HCID 118248863, compound

HRID 1775445Notes

Reaction equation

HRID 1775445 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C:11]1[C:19]2[C:14](=[CH:15][C:16]([Cl:23])=[C:17]3[O:22][CH2:21][CH2:20][C:18]3=2)[NH:13][C:12]=1[C:24]([OH:26])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O[C:32]([NH:34]CCC1C2C(Cl)=C3OCCC3=CC=2NC=1C(O)=O)=O)(C)(C)C.C(N(C(C)C)CC)(C)C.Cl.CN.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>O.CN(C)C=O>[Cl:23][C:16]1[CH:15]=[C:14]2[C:19]([C:11]([CH2:10][CH2:9][NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[C:12]([C:24](=[O:26])[NH:34][CH3:32])[NH:13]2)=[C:18]2[CH2:20][CH2:21][O:22][C:17]=12

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 6364545Methylamine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118071477HCID 118071477, compoundHCID 118071520HCID 118071520, compound

Product 1

HCID 118248863HCID 118248863, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of a mixture (1.85 g) of 8-{2-[(tert-butoxycarbonyl)amino]ethyl}-4-chloro-1,6-dihydro-2H-furo[3,2-e]indole-7-carboxylic acid and 7-{2-[(tert-butoxycarbonyl)amino]ethyl}-8-chloro-3,5-dihydro-2H-furo[2,3-f]indole-6-carboxylic acid, and diisopropylethylamine (4.16 mL), methylamine hydrochloride (988 mg), and N,N-dimethyl formamide (37.0 mL) was added 2-(7-aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (2.77 g), followed by stirring at room temperature overnight. To the mixture was added water under ice-cooling, and the precipitated solid was collected by filtration and dried under reduced pressure to obtain a yellowish brown solid. This was purified by silica gel column chromatography (toluene:chloroform:methanol=5:4:0 to toluene:chloroform:methanol=50:40:6) to obtain tert-butyl {2-[4-chloro-7-(methylcarbamoyl)-1,6-dihydro-2H-furo[3,2-e]indol-8-yl]ethyl}carbamate (213 mg) of a high-polarity fraction as a compound of Preparation Example 26. Further, the low-polarity fraction was concentrated under reduced pressure and the obtained residue was solidified with ethanol to obtain a yellow solid of tert-butyl {2-[8-chloro-6-(methylcarbamoyl)-3,5-dihydro-2H-furo[2,3-f]indol-7-yl]ethyl}carbamate (750 mg) as a compound of Preparation Example 66 as shown in the table below.

Workup

  1. temperaturecooling
  2. filtrationthe precipitated solid was collected by filtration
  3. customdried under reduced pressure
  4. customto obtain a yellowish brown solid
  5. customThis was purified by silica gel column chromatography (toluene:chloroform:methanol=5:4:0 to toluene:chloroform:methanol=50:40:6)

Sources & evidence

ORD record
ord-4ba2cda2a5564dec9fa09cd9998e4dd4
Source dataset
uspto-grants-2016_02
Patent number
US09260445B2

Reaction notes

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