1-(1H-indol-3-yl)-2-methylpropan-2-amine → (E)-methyl 3-(4-(3,3-dimethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)-3,5-difluorophenyl)acrylate

HRID 1749030Notes

Reaction equation

[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C:11]([CH3:14])([NH2:13])[CH3:12])=[CH:2]1.[F:15][C:16]1[CH:17]=[C:18](/[CH:25]=[CH:26]/[C:27]([O:29][CH3:30])=[O:28])[CH:19]=[C:20]([F:24])[C:21]=1[CH:22]=O>C(O)(=O)C>[CH3:12][C:11]1([CH3:14])[NH:13][CH:22]([C:21]2[C:20]([F:24])=[CH:19][C:18](/[CH:25]=[CH:26]/[C:27]([O:29][CH3:30])=[O:28])=[CH:17][C:16]=2[F:15])[C:2]2[NH:1][C:9]3[C:4]([C:3]=2[CH2:10]1)=[CH:5][CH:6]=[CH:7][CH:8]=3

Participants

Conditions

Temperature: 80 °C

Procedure

1-(1H-Indol-3-yl)-2-methylpropan-2-amine (807 mg, 4.29 mmol) and (E)-methyl 3-(3,5-difluoro-4-formylphenyl)acrylate (obtained as described in Example 1, preparation of starting materials) (970 mg, 4.29 mmol) were combined in acetic acid (15 ml) and the mixture heated to 80° C. for 2 hours. The reaction mixture was purified by ion exchange chromatography, using an SCX-2 column. The desired product was eluted from the column using 2M NH3 in methanol and product-containing fractions were evaporated to dryness to afford (E)-methyl 3-(4-(3,3-dimethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)-3,5-difluorophenyl)acrylate (1610 rag, 95%) as a yellow foam. 1H NMR (500 MHz, DMSO, 20° C.) δ 1.15 (3H, s), 1.27 (3H, s), 2.23 (1H, s), 2.61 (2H, s), 3.75 (3H, s), 5.46 (1H, s), 6.84 (1H, d), 6.97 (2H, dtd), 7.18 (1H, d), 7.39 (1H, d), 7.58 (2H, s), 7.67 (1H, d), 10.60 (1H, s). m/z: ES− [M−H]− 395.

Workup

customThe reaction mixture was purified by ion exchange chromatography
washThe desired product was eluted from the column
additionproduct-containing fractions
customwere evaporated to dryness

Sources & evidence

ORD record: ord-4a7b6b8a56e9475c84ba21dd44bb005e
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09155727B2

Reaction notes

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