Sodium Hydroxide → HCID 86345430, compound

HRID 1749021Notes

Reaction equation

HRID 1749021 reaction equation
[OH-].[Na+].[F:3][C:4]([CH3:33])([CH3:32])[CH2:5][N:6]1[C@H:18]([CH3:19])[CH2:17][C:16]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[NH:9][C:8]=2[C@H:7]1[C:20]1[CH:25]=[CH:24][C:23](/[CH:26]=[CH:27]/[C:28]([O:30]C)=[O:29])=[CH:22][CH:21]=1>CO>[F:3][C:4]([CH3:32])([CH3:33])[CH2:5][N:6]1[C@H:18]([CH3:19])[CH2:17][C:16]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[NH:9][C:8]=2[C@H:7]1[C:20]1[CH:21]=[CH:22][C:23](/[CH:26]=[CH:27]/[C:28]([OH:30])=[O:29])=[CH:24][CH:25]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 117719352HCID 117719352, compound

Product 1

HCID 86345430HCID 86345430, compoundYield 21.02%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
20 °C

Procedure

7.5M Sodium hydroxide solution (0.983 ml, 7.37 mmol) was added to a solution of (E)-methyl 3-(4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylate (310 mg, 0.74 mmol) in methanol (5 ml). The mixture was stirred at 20° C. for 2 hours. The reaction mixture was purified by ion exchange chromatography, using an SCX-2 column. Fractions containing the desired product were eluted from the column using 7M NH3/methanol and pure fractions were evaporated to dryness to afford a yellow solid. The crude product was purified by preparative HPLC (Waters SunFire column, 5μ silica, 50 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 0.1% formic acid) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness and then loaded onto SCX-2 column and eluted with 7N ammonia in methanol to afford the title product (63.0 mg, 21.02%) as a yellow solid. 1H NMR (400 MHz, DMSO, 30° C.) δ 1.06 (3H, d), 1.30 (3H, d), 1.47 (3H, d), 2.53-2.64 (2H, m), 2.79 (2H, s), 3.10 (1H, d), 5.08 (1H, s), 6.47 (1H, d), 6.98 (1H, t), 7.06 (1H, t), 7.19-7.37 (3H, m), 7.44 (1H, d), 7.56 (1H, d), 7.63 (2H, d), 10.81 (1H, s), 12.30 (1H, s). m/z: ES+ [M+H]+ 407.

Workup

  1. customThe reaction mixture was purified by ion exchange chromatography
  2. additionFractions containing the desired product
  3. washwere eluted from the column
  4. customwere evaporated to dryness
  5. customto afford a yellow solid
  6. customThe crude product was purified by preparative HPLC (Waters SunFire column, 5μ silica, 50 mm diameter, 100 mm length)
  7. additionFractions containing the desired compound
  8. customwere evaporated to dryness
  9. washeluted with 7N ammonia in methanol

Sources & evidence

ORD record
ord-50d4faeeb3b246c48c18640e625f747c
Source dataset
uspto-grants-2015_10
Patent number
US09155727B2

Reaction notes

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