Sodium Hydroxide → HCID 86342655, compound

HRID 1749034Notes

Reaction equation

HRID 1749034 reaction equation
[OH-].[Na+].[F:3][C:4]([CH3:34])([CH3:33])[CH2:5][N:6]1[C:18]([CH3:20])([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[CH:7]1[C:21]1[CH:26]=[CH:25][C:24](/[CH:27]=[CH:28]/[C:29]([O:31]C)=[O:30])=[CH:23][CH:22]=1>CO.O>[F:3][C:4]([CH3:34])([CH3:33])[CH2:5][N:6]1[C:18]([CH3:20])([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[CH:7]1[C:21]1[CH:26]=[CH:25][C:24](/[CH:27]=[CH:28]/[C:29]([OH:31])=[O:30])=[CH:23][CH:22]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 117719369HCID 117719369, compound

Product 1

HCID 86342655HCID 86342655, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
22 °C

Procedure

2M Sodium hydroxide solution (0.782 ml, 1.56 mmol) was added to a solution of (E)-methyl 3-(4-(2-(2-fluoro-2-methylpropyl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylate (isomer 1) (68 mg, 0.16 mmol) in methanol (5 ml) THF (5.00 ml) and water (5.00 ml) and the mixture stirred for 40 hours at 22° C. The mixture was concentrated to a volume such that all of the organic solvent had been removed and was acidified to pH6 with 2M HCl. Concentrated aqueous ammonia (2 drops) was added, followed by methanol (˜2 ml), giving a pale yellow solution. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the title product (isomer 1) (50.0 mg, 76%) as a yellow solid. 1H NMR (500 MHz, DMSO, 30° C.) δ 0.93 (3H, s), 1.19 (3H, d), 1.23 (3H, s), 1.51 (3H, d), 2.56-2.64 (2H, m), 2.75 (1H, d), 3.04 (1H, dd), 5.06 (1H, s), 6.40 (1H d), 7.03 (1H, ddd), 7.09-7.15 (2H, m), 7.35 (1H, dd), 7.44-7.51 (5H, m), 10.87 (1H, s), CO2H not observed. m/z: ES+ [M+H]+ 421. *Stereochemistry inferred to be (R) at the undefined centre by analogy with other examples.

Workup

  1. concentrationThe mixture was concentrated to a volume such that all of the organic solvent
  2. customhad been removed
  3. additionConcentrated aqueous ammonia (2 drops) was added
  4. customgiving a pale yellow solution
  5. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 100 mm length)
  6. additionFractions containing the desired compound
  7. customwere evaporated to dryness

Sources & evidence

ORD record
ord-3167da0608e5417da9001b0d1eb9207a
Source dataset
uspto-grants-2015_10
Patent number
US09155727B2

Reaction notes

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