Sodium Carbonate → Methyl 2-(4-(tert-butoxycarbonyl)pyridin-3-yl)-3-cyclohexyl-1H-indole-6-carboxylate

HRID 860734Notes

Reaction equation

HRID 860734 reaction equation
[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:13][CH:14]=3)[NH:9][C:8]=2B2OC(C)(C)C(C)(C)O2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br[C:30]1[CH:31]=[N:32][CH:33]=[CH:34][C:35]=1NC(=O)OC(C)(C)C.[Li+].[Cl-].[C:46]([O-:49])([O-])=[O:47].[Na+].[Na+]>C(O)C.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.C1(C)C=CC=CC=1>[C:1]([O:49][C:46]([C:35]1[CH:30]=[CH:31][N:32]=[CH:33][C:34]=1[C:8]1[NH:9][C:10]2[C:15]([C:7]=1[CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)=[CH:14][CH:13]=[C:12]([C:16]([O:18][CH3:19])=[O:17])[CH:11]=2)=[O:47])([CH3:7])([CH3:6])[CH3:2]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 10707388tert-Butyl (3-bromopyridin-4-yl)carbamateHCID 23152432methyl 3-cyclohexyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-6-carboxylate

Product 1

HCID 69207220Methyl 2-(4-(tert-butoxycarbonyl)pyridin-3-yl)-3-cyclohexyl-1H-indole-6-carboxylateYield 78.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of methyl 3-cyclohexyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-6-carboxylate (383 mg, 1.0 mmol), tert-butyl 3-bromopyridin-4-ylcarbamate (328 mg, 1.2 mmol) and LiCl (84.8 mg, 2.0 mmol), in ethanol (3 mL) and toluene (3 mL) was added, 2M aqueous Na2CO3 (1.25 mL, 2.5 mmol) solution. The mixture was then degassed by the application of vacuum followed by flushing with N2.Pd(PPh3)4 (58 mg, 0.05 mmol) was then added and the reaction was heated at 80° C. overnight. The resultant mixture was then filtered and concentrated under vacuum, and the product residue was purified by Prep. reverse phase HPLC to afford the title compound as an off-white solid, (170 mg, 38% yield). MS m/z 450(MH+); 1H NMR (300 MHz, CDCl3) δ ppm 1.15–1.33 (m, 13 H) 1.63–1.98 (m, 6 H) 2.45 (m, 1 H) 3.92 (s, 3 H) 6.94 (s, 1 H) 7.75–7.89 (m, 2 H) 8.17 (s, 1 H) 8.21 (d, J=5.86 Hz, 1 H) 8.37 (s, 1 H) 8.45 (d, J=5.86 Hz, 1 H) 9.45 (s, 1 H).

Workup

  1. customThe mixture was then degassed by the application of vacuum
  2. customby flushing with N2
  3. filtrationThe resultant mixture was then filtered
  4. concentrationconcentrated under vacuum
  5. customthe product residue was purified by Prep

Sources & evidence

ORD record
ord-8a01605fa0434d93a1b4624518345efe
Source dataset
uspto-grants-2006_12
Patent number
US07153848B2

Reaction notes

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