Potassium Carbonate → 7-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-3-{1-[(3S)-pyrrolidin-3-yl]-1H-pyrazol-4-yl}furo[3,2-c]pyridin-6-amine

HRID 911983Notes

Reaction equation

HRID 911983 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(OC([N:31]1[CH2:35][CH2:34][C@H:33]([N:36]2[CH:40]=[C:39](B3OC(C)(C)C(C)(C)O3)[CH:38]=[N:37]2)[CH2:32]1)=O)(C)(C)C.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[Cl:22][C:15]1[C:16]([F:21])=[CH:17][CH:18]=[C:19]([Cl:20])[C:14]=1[C@H:12]([O:11][C:10]1[C:5]2[O:4][CH:3]=[C:2]([C:39]3[CH:38]=[N:37][N:36]([C@H:33]4[CH2:34][CH2:35][NH:31][CH2:32]4)[CH:40]=3)[C:6]=2[CH:7]=[N:8][C:9]=1[NH2:23])[CH3:13]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 57812584(S)-(1-(1-(tert-Butoxycarbonyl)pyrrolidin-3-yl)-1H-pyrazol-4-yl)boronic acid pinacol esterHCID 578127253-Bromo-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-6-ylamine

Product 1

HCID 578127707-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-3-{1-[(3S)-pyrrolidin-3-yl]-1H-pyrazol-4-yl}furo[3,2-c]pyridin-6-amine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3-bromo-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-6-ylamine (20 mg, 0.048 mmol), (S)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]pyrrolidine-1-carboxylic acid tert-butyl ester (26 mg, 0.071 mmol) and potassium carbonate (20 mg, 0.10 mmol) in 1,4-dioxane (2 mL) and H2O (0.5 mL) was stirred at 100° C. for 30 min in the microwave reactor. Then, the mixture was passed through PL-Thiol MP SPE+ resin and concentrated in vacuo. The resulting solid was left to stir in DCM (0.2 mL) and TFA (0.2 mL) at rt for 30 min. Purification via MDP afforded the title compound as a white solid. MS (ES+): m/z: 475.96/477.94 (70/50) [MH+]. HPLC: tR=2.35 min (ZQ3, polar—5 min). 1H NMR (400 MHz, CD3OD): δ 1.89 (d, J=6.6 Hz, 3H), 2.40 (ddd, J=13.9, 7.6, 3.3 Hz, 1H), 2.50-2.62 (m, 1H), 3.50 (ddd, J=11.5, 8.8, 4.4 Hz, 1H), 3.63-3.73 (m, 2H), 3.75-3.82 (m, 1H), 5.28 (q, J=6.4 Hz, 1H), 6.53 (q, J=6.8 Hz, 1H), 7.21 (t, J=8.6 Hz, 1H), 7.39 (dd, J=8.9, 4.9 Hz, 1H), 7.79 (s, 1H), 7.89 (s, 1H), 8.14 (d, J=4.8 Hz, 2H).

Workup

  1. concentrationconcentrated in vacuo
  2. waitThe resulting solid was left
  3. stirringto stir in DCM (0.2 mL)
  4. waitTFA (0.2 mL) at rt for 30 min
  5. customPurification via MDP

Sources & evidence

ORD record
ord-78f0e783749e42959e55e8b808df345b
Source dataset
uspto-grants-2011_09
Patent number
US08022206B2

Reaction notes

Loading…