Triethylamine → 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(6-fluoro-1,1-dimethyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-7-yl)cyclopropanecarboxamide

HRID 1847927Notes

Reaction equation

HRID 1847927 reaction equation
[F:1][C:2]1([F:17])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([OH:16])=O)[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1.[F:18][C:19]1[C:20]([NH2:33])=[CH:21][C:22]2[CH:23]=[C:24]3[C:30]([CH3:32])([CH3:31])[CH2:29][CH2:28][N:25]3[C:26]=2[CH:27]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C>[F:17][C:2]1([F:1])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:33][C:20]4[C:19]([F:18])=[CH:27][C:26]5[N:25]6[CH2:28][CH2:29][C:30]([CH3:32])([CH3:31])[C:24]6=[CH:23][C:22]=5[CH:21]=4)=[O:16])[CH2:12][CH2:13]3)=[CH:10][C:4]=2[O:3]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 442061031-(2,2-Difluoro-1,3-benzodioxol-5-yl)cyclopropanecarboxylic acidHCID 581832876-fluoro-1,1-dimethyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-7-amine

Product 1

HCID 591294801-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(6-fluoro-1,1-dimethyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-7-yl)cyclopropanecarboxamideYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxylic acid (346 mg, 1.4 mmol), 6-fluoro-1,1-dimethyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-7-amine (260 mg, 1.2 mmol) and HATU (543 mg, 1.4 mmol) in DMF (5 mL) was added triethylamine (0.40 mL, 2.9 mmol). The reaction was stirred at room temperature overnight and then partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with brine and dried over MgSO4. After the removal of solvent, the residue was purified by column chromatography (10-20% ethyl acetate-hexanes) to afford 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(6-fluoro-1,1-dimethyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-7-yl)cyclopropanecarboxamide (342 mg, 65%). ESI-MS m/z calc. 442.2. found 443.5 (M+1)+. Retention time 2.30 minutes. 1H NMR (400 MHz, DMSO-d6) δ 8.20 (d, J=7.6 Hz, 1H), 7.30-7.25 (m, 3H), 7.20 (m, 1H), 7.12 (d, J=8.2 Hz, 1H), 6.84 (d, J=11.1 Hz, 1H), 6.01 (d, J=0.5 Hz, 1H), 3.98 (t, J=6.8 Hz, 2H), 2.37 (t, J=6.8 Hz, 2H), 1.75 (dd, J=3.8, 6.9 Hz, 2H), 1.37 (s, 6H) and 1.14 (dd, J=3.9, 6.9 Hz, 2H) ppm.

Workup

  1. custompartitioned between ethyl acetate and water
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. customAfter the removal of solvent
  6. customthe residue was purified by column chromatography (10-20% ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-5fd5acac25e74a489ee543fe5fb96d8b
Source dataset
uspto-grants-2015_02
Patent number
US08952049B2

Reaction notes

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