Sodium Bicarbonate → 6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-2-(2,4-dimethoxybenzyl)-7-fluoro-4-(pyrazolo[1,5-a]pyridin-3-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one

HRID 516091Notes

Reaction equation

HRID 516091 reaction equation
[NH2:1][C@@H:2]1[C@H:7]([NH:8][C:9]2[N:14]=[C:13](Cl)[C:12]3[C:16](=[O:30])[N:17]([CH2:19][C:20]4[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][C:21]=4[O:28][CH3:29])[CH2:18][C:11]=3[C:10]=2[F:31])[CH2:6][CH2:5][O:4][CH2:3]1.[N:32]1[N:36]2[CH:37]=[CH:38][CH:39]=[CH:40][C:35]2=[C:34](B(O)O)[CH:33]=1.C([O-])(O)=O.[Na+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:1][C@@H:2]1[C@H:7]([NH:8][C:9]2[N:14]=[C:13]([C:34]3[CH:33]=[N:32][N:36]4[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=34)[C:12]3[C:16](=[O:30])[N:17]([CH2:19][C:20]4[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][C:21]=4[O:28][CH3:29])[CH2:18][C:11]=3[C:10]=2[F:31])[CH2:6][CH2:5][O:4][CH2:3]1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 55255152Pyrazolo[1,5-A]pyridin-3-ylboronic acidHCID 866547386-((3R,4R)-3-aminotetrahydro-2H-pyran-4-ylamino)-4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one

Product 1

HCID 672382796-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-2-(2,4-dimethoxybenzyl)-7-fluoro-4-(pyrazolo[1,5-a]pyridin-3-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-oneYield 100.7%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a 5 mL microwave vial with a stir bar was added bis(triphenylphosphine)palladium chloride (11.68 mg, 0.017 mmol), 6-((3R,4R)-3-aminotetrahydro-2H-pyran-4-ylamino)-4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one (75 mg, 0.166 mmol), pyrazolo[1,5-a]pyridin-3-ylboronic acid (135 mg, 0.832 mmol) in dioxane (2 mL), and saturated aq NaHCO3 (2 mL). The mixture was heated in a Biotage Initiator microwave at 120° C. for 30 min. The mixture was concentrated and purified via preparative HPLC to give the title compound (89 mg, 100%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.82-1.84 (m, 1 H), 2.10-2.12 (m, 1 H), 3.68-3.72 (m, 3 H), 3.75 (s, 3 H), 3.82 (s, 3 H), 3.92-3.95 (m, 1 H), 4.01-4.02 (m, 1 H), 4.39 (s, 2 H), 4.55-4.58 (m, 1 H), 4.59 (s, 2 H), 6.50 (dd, J=8.30, 1.95 Hz, 1 H), 6.60 (d, J=2.44, 1 H), 7.04-7.08 (m, 2 H), 7.16 (d, J=5.86 Hz, 1 H), 7.48-7.51 (m, 1 H), 7.93 (br s, 1 H), 8.37 (d, J=9.27 Hz, 1 H), 8.79 (d, J=6.83 Hz, 1 H), 9.36 (s, 1 H). [M+H] calc'd for C28H29FN6O4, 533; found, 533.

Workup

  1. concentrationThe mixture was concentrated
  2. custompurified via preparative HPLC

Sources & evidence

ORD record
ord-3cd19f71878843728a0c229f59733f41
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Reaction notes

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