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 1847927ノート

反応式

HRID 1847927 の反応式
[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

参加物

6

反応物 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

生成物 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)cyclopropanecarboxamide収率 65%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-5fd5acac25e74a489ee543fe5fb96d8b
出典データセット
uspto-grants-2015_02
特許番号
US08952049B2

反応ノート

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