Sodium Bicarbonate → HCID 86658596, compound

HRID 1400888Notes

Reaction equation

HRID 1400888 reaction equation
[CH:1]1([NH:4][C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22](I)[S:23][C:16]=34)=[C:10]([F:25])[CH:9]=2)=[O:6])[CH2:3][CH2:2]1.[C:26]([N:33]1[CH2:38][CH:37]=[C:36](B2OC(C)(C)C(C)(C)O2)[CH2:35][CH2:34]1)([O:28][C:29]([CH3:32])(C)C)=[O:27].C([O-])(O)=O.[Na+].CO[CH2:55][CH2:56]OC.O>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>[CH:1]1([NH:4][C:5](=[O:6])[NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:36]5[CH2:35][CH2:34][N:33]([C:26]([O:28][CH2:29][CH2:32][CH2:55][CH3:56])=[O:27])[CH2:38][CH:37]=5)[S:23][C:16]=34)=[C:10]([F:25])[CH:9]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 18180031Water 1,2-dimethoxyethaneHCID 67443712HCID 67443712, compound

Product 1

HCID 86658596HCID 86658596, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

Iodide 269 (2 g, 4.26 mmol), 1-N-Boc-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine (1.85 g, 5.96 mmol), NaHCO3 (1.1 g, 12.8 mmol) and tetrakis(triphenylphosphine)palladium (0.49 g, 0.43 mmol) were suspended in a mixture of DME/water (80 mL/16 mL). The mixture was degassed with an Ar flow, heated at 80° C. and stirred for 16 hours. The mixture was then cooled and filtered through a pad of Celite and washed with EtOAc. The filtrate was diluted with water and extracted with EtOAc. The extract was washed with brine, dried over anhydrous MgSO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel (eluent 3% MeOH in DCM) to afford title compound 270 (1.7 g, 78% yield) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ (ppm): 8.73 (s, 1H), 8.45 (d, J=5.4 Hz, 1H), 7.72 (dd, J=13.5, 2.4 Hz, 1H), 7.55 (s, 1H), 7.35 (t, J=9.0 Hz, 1H), 7.24-7.16 (m, 1H), 6.60 (br, 1H), 6.57 (d, =5.4 Hz, 1H), 6.40 (br, 1H), 4.15-4.00 (m, 2H), 3.63-3.54 (m, 2H), 2.70-2.40 (m, 3H), 1.44 (s, 9H), 0.70-0.60 (m, 2H), 0.48-0.35 (m, 2H).

Workup

  1. customThe mixture was degassed with an Ar flow
  2. temperatureThe mixture was then cooled
  3. filtrationfiltered through a pad of Celite
  4. washwashed with EtOAc
  5. additionThe filtrate was diluted with water
  6. extractionextracted with EtOAc
  7. washThe extract was washed with brine
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by flash chromatography on silica gel (eluent 3% MeOH in DCM)

Sources & evidence

ORD record
ord-7de8ca37f5664e1eb689ae84445c6a3a
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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