Potassium Carbonate → 4-{6-amino-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-3-yl}-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

HRID 911955Notes

Reaction equation

HRID 911955 reaction equation
Br[C:2]1[C:6]2[CH:7]=[N:8][C:9]([NH2:23])=[C:10]([O:11][C@@H:12]([C:14]3[C:19]([Cl:20])=[CH:18][CH:17]=[C:16]([F:21])[C:15]=3[Cl:22])[CH3:13])[C:5]=2[O:4][CH:3]=1.[C:24]([O:28][C:29]([N:31]1[CH2:36][CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25].C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>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.O>[C:24]([O:28][C:29]([N:31]1[CH2:32][CH:33]=[C:34]([C:2]2[C:6]3[CH:7]=[N:8][C:9]([NH2:23])=[C:10]([O:11][C@@H:12]([C:14]4[C:19]([Cl:20])=[CH:18][CH:17]=[C:16]([F:21])[C:15]=4[Cl:22])[CH3:13])[C:5]=3[O:4][CH:3]=2)[CH2:35][CH2:36]1)=[O:30])([CH3:27])([CH3:25])[CH3:26]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 578127253-Bromo-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-6-ylamine

Product 1

HCID 578125254-{6-amino-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-3-yl}-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

A mixture of 3-bromo-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)-ethoxy]-furo[3,2-c]pyridin-6-ylamine (100.0 mg, 0.2381 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (88.3 mg, 0.286 mmol), Pd(PPh3)4 (10 mg, 0.01 mmol), potassium carbonate (98.7 mg, 0.714 mmol) and 4:1 dioxane:water (4 mL) was microwaved at 100° C. for 2 h. The solution was concentrated in vacuo, and dry-loaded onto silica gel for column chromatography, eluted with 2-5% MeOH in DCM. Fractions containing the product were concentrated in vacuo to afford the title compound as an off-white solid. 1H NMR (CD3OD, 400 MHz): δ=1.49 (s, 9H), 1.88 (d, J=6.8 Hz, 3H), 2.48 (d, J=1.5 Hz, 2H), 3.59-3.69 (m, 2H), 4.11 (br, s, 2H), 6.26 (br, s, 1H), 6.50 (q, J=6.9 Hz, 1H), 7.19-7.25 (m, 1H), 7.40 (dd, J=9.0, 4.9 Hz, 1H), 7.64 (s, 1H), 8.20 (s, 1H). MS (ES+): m/z 522.14 [MH+]. HPLC: tR=3.51 min (ZQ3, polar—5 min).

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. washdry-loaded onto silica gel for column chromatography, eluted with 2-5% MeOH in DCM
  3. additionFractions containing the product
  4. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-25fb28e6caab4397ae00795b5226d3ea
Source dataset
uspto-grants-2011_09
Patent number
US08022206B2

Reaction notes

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