Methyl 6-bromopyridine-2-carboxylate → HCID 11951624, compound

HRID 2423551Notes

Reaction equation

HRID 2423551 reaction equation
[CH3:1][C:2]([CH3:29])([CH3:28])[CH2:3][N:4]1[C:12]2[C:7](=[C:8]([CH2:25][CH2:26][CH3:27])[C:9]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([Sn](C)(C)C)[CH:16]=3)=[CH:10][CH:11]=2)[CH:6]=[CH:5]1.Br[C:31]1[N:36]=[C:35]([C:37]([O:39]C)=[O:38])[CH:34]=[CH:33][CH:32]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][C:2]([CH3:29])([CH3:28])[CH2:3][N:4]1[C:12]2[C:7](=[C:8]([CH2:25][CH2:26][CH3:27])[C:9]([O:13][CH2:14][C:15]3[CH:16]=[C:17]([C:31]4[N:36]=[C:35]([C:37]([OH:39])=[O:38])[CH:34]=[CH:33][CH:32]=4)[CH:18]=[CH:19][CH:20]=3)=[CH:10][CH:11]=2)[CH:6]=[CH:5]1

Participants

4

Reactant 2

HCID 16217886Methyl 6-bromopyridine-2-carboxylateHCID 67240968HCID 67240968, compound

Product 1

HCID 11951624HCID 11951624, compound

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
110 °C

Procedure

1-(Bromomethyl)-3-iodobenzene was used to alkylate 1-(2,2-dimethyl-propyl)-4-propyl-1H-indol-5-ol following the procedure outlined in example 1. A mixture of the above indole (3.4 g, 7.3 mmol), hexamethyldistannane (5.0 g, 15 mmol), Pd(PPh3)4 (0.80 g, 0.69 mmol), and THF (40 mL) was heated at 60° C. for 18 h under N2 and then allowed to cool to rt. The reaction mixture was diluted with water and extracted with ethyl acetate (×3). The organic extracts were dried (Na2SO4), filtered, concentrated, and purified by silica gel chromatography to give 1-(2,2-dimethylpropyl)-4-propyl-5-{[3-(trimethylstannyl)-benzyl]oxy}-1H-indole as a yellow oil. A mixture of the above stannane (0.35 g, 0.70 mmol), methyl 6-bromopyridine-2-carboxylate (0.22 g, 1.0 mmol), Pd(PPh3)4 (0.10 g, 87 μmol), and degassed toluene (10 mL) was heated at 110° C. for 24 h under N2 and then allowed to cool to rt. The reaction mixture was purified by silica gel chromatography (hexanes:ethyl acetate—1:0→2:1) to give a yellow oil. MS (ESI): 471.1 (M+H). A similar procedure as outlined in example 26 was followed for the saponification of the above ester. 1H NMR (DMSO, 500 MHz) 13.18 (br s, 1H), 8.31 (s, 1H), 8.19 (d, 1H), 8.12 (d, 1H), 8.09 (t, 1H), 8.01 (d, 1H), 7.61-7.53 (m, 2H), 7.28 (d, 1H), 7.23 (d, 1H), 7.00 (d, 1H), 6.40 (d, 1H), 5.19 (s, 2H), 3.91 (s, 2H), 2.84 (t, 2H), 1.68-1.58 (m, 2H), 0.93 (s, 9H), 0.91 (t, 3H). MS (ESI): 457.1 (M+H).

Workup

  1. customdegassed toluene (10 mL)
  2. temperatureto cool to rt
  3. customThe reaction mixture was purified by silica gel chromatography (hexanes:ethyl acetate—1:0→2:1)
  4. customto give a yellow oil

Sources & evidence

ORD record
ord-ad032e66d46f4ee9ab6254353d1ee452
Source dataset
uspto-grants-2011_06
Patent number
US07960417B2

Reaction notes

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