Sodium Bicarbonate → HCID 90281470, compound

HRID 2170372Notes

Reaction equation

HRID 2170372 reaction equation
Br[C:2]1[C:3]([C@@H:13]([NH:23][C:24](=[O:41])[CH2:25][N:26]2[C:30]3[C:31]([F:36])([F:35])[C@@H:32]4[CH2:34][C@@H:33]4[C:29]=3[C:28]([C:37]([F:40])([F:39])[F:38])=[N:27]2)[CH2:14][C:15]2[CH:20]=[C:19]([F:21])[CH:18]=[C:17]([F:22])[CH:16]=2)=[N:4][CH:5]=[C:6]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])[CH:7]=1.[CH3:42][C:43]1[N:48]2[C:49](=[O:52])[NH:50][N:51]=[C:47]2[CH:46]=[CH:45][C:44]=1B1OC(C)(C)C(C)(C)O1.C(=O)(O)[O-].[Na+]>C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.Cl[Pd]Cl.O1CCOCC1>[F:36][C:31]1([F:35])[C:30]2[N:26]([CH2:25][C:24]([NH:23][C@H:13]([C:3]3[C:2]([C:44]4[CH:45]=[CH:46][C:47]5[N:48]([C:49](=[O:52])[NH:50][N:51]=5)[C:43]=4[CH3:42])=[CH:7][C:6]([NH:8][S:9]([CH3:12])(=[O:10])=[O:11])=[CH:5][N:4]=3)[CH2:14][C:15]3[CH:20]=[C:19]([F:21])[CH:18]=[C:17]([F:22])[CH:16]=3)=[O:41])[N:27]=[C:28]([C:37]([F:40])([F:38])[F:39])[C:29]=2[C@H:33]2[CH2:34][C@@H:32]12

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 90281336HCID 90281336, compoundHCID 90281516HCID 90281516, compound

Product 1

HCID 90281470HCID 90281470, compound

Reagents, catalysts & solvents 2

HCID 11050900Dichlorobis(tricyclohexylphosphine)pallium (II)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
170 °C

Procedure

A microwave tube was charged with N—((S)-1-(3-bromo-5-(methylsulfonamido)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2-((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamide (41D, 20 mg, 0.03 mmol), 5-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (12.3 mg, 0.045 mmol) and PdCl2[P(Cy)3]2 (2.2 mg, 0.003 mmol). To the mixture was added 0.6 mL of 1,4-dioxane and 0.09 mL of sodium bicarbonate aqueous solution (1M). The system was purged with argon and then the microwave tube was sealed and the reaction mixture was heated in a microwave synthesizer at 170° C. for 15 min. After cooling, the reaction was partitioned between EtOAc and water. The organic layer was separated and washed with brine, then dried over MgSO4, filtered and concentrated. The residue was purified by reverse phase HPLC eluting with acetonitrile and water (with 0.1% TFA) to afford the title compound. 1H NMR (400 MHz, methanol-d4) δ 8.91-8.48 (m, 1H), 7.40 (dd, J=13.1, 2.6 Hz, 1H), 7.07-5.77 (m, 5H), 5.38-5.02 (m, 1H), 4.85 (s, 2H), 3.29-2.92 (m, 5H), 2.66-1.95 (m, 5H), 1.41 (dd, J=8.1, 6.0 Hz, 1H), 1.10 (m, 1H). MS (m/z) 738.92 [M+H]+.

Workup

  1. customThe system was purged with argon
  2. customthe microwave tube was sealed
  3. temperatureAfter cooling
  4. customthe reaction was partitioned between EtOAc and water
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by reverse phase HPLC
  11. washeluting with acetonitrile and water (with 0.1% TFA)

Sources & evidence

ORD record
ord-b45cb73faa4a4b79a32ed37595565463
Source dataset
uspto-grants-2015_06
Patent number
US09050344B2

Reaction notes

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