Sodium Carbonate → 5-{2-[4-(Morpholine-4-sulfonyl)-phenyl]-imidazo[2,1-b][1,3,4]thiadiazol-5-yl}-3-trifluoromethyl-pyridin-2-ylamine

HRID 2409586Notes

Reaction equation

HRID 2409586 reaction equation
I[C:2]1[N:9]2[C:5]([S:6][C:7]([C:10]3[CH:15]=[CH:14][C:13]([S:16]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)(=[O:18])=[O:17])=[CH:12][CH:11]=3)=[N:8]2)=[N:4][CH:3]=1.CC1(C)C(C)(C)OB([C:33]2[CH:34]=[C:35]([C:40]([F:43])([F:42])[F:41])[C:36]([NH2:39])=[N:37][CH:38]=2)O1.C([O-])([O-])=O.[Na+].[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>[N:19]1([S:16]([C:13]2[CH:14]=[CH:15][C:10]([C:7]3[S:6][C:5]4=[N:4][CH:3]=[C:2]([C:33]5[CH:34]=[C:35]([C:40]([F:43])([F:42])[F:41])[C:36]([NH2:39])=[N:37][CH:38]=5)[N:9]4[N:8]=3)=[CH:11][CH:12]=2)(=[O:18])=[O:17])[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 468641035-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)pyridin-2-amineHCID 667171205-Iodo-2-[4-(morpholine-4-sulfonyl)-phenyl]-imidazo[2,1-b][1,3,4]thiadiazole

Product 1

HCID 469411315-{2-[4-(Morpholine-4-sulfonyl)-phenyl]-imidazo[2,1-b][1,3,4]thiadiazol-5-yl}-3-trifluoromethyl-pyridin-2-ylamineYield 34%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 5-Iodo-2-[4-(morpholine-4-sulfonyl)-phenyl]-imidazo[2,1-b][1,3,4]thiadiazole (85 mg, 0.18 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3-trifluoromethyl-pyridin-2-ylamine (60 mg, 0.27 mmol), PdCl2(PPh3)2 (26 mg, 0.037 mmol) and 2M aq Na2CO3 (0.5 mL) in dioxane (4 mL) was heated at 90° C. for 18 h. On cooling, the solvents were removed in vacuo and the residue was triturated from EtOAc and filtered off. The filtrate was evaporated and the residue was recrystallyzed from MeOH, filtered and washed with water. The solid was purified by column chromatography (DCM/MeOH) to afford the desired product (31 mg, 34%) as a yellow solid. HPLC-MS (5-100% B in 8 min at 0.8 mL): tR=5.12 min, [M+H]+ m/z 511.2; 1H NMR (300 MHz, DMSO) δ 8.89 (s, 1H), 8.36 (s, 1H), 8.26 (d, J=8.3 Hz, 2H), 7.97 (d, J=8.3 Hz, 2H), 7.84 (s, 1H), 6.77 (s, 2H), 3.65 (s, 4H), 2.95 (s, 4H).

Workup

  1. temperatureOn cooling
  2. customthe solvents were removed in vacuo
  3. customthe residue was triturated from EtOAc
  4. filtrationfiltered off
  5. customThe filtrate was evaporated
  6. filtrationfiltered
  7. washwashed with water
  8. customThe solid was purified by column chromatography (DCM/MeOH)

Sources & evidence

ORD record
ord-c10005acfb53436f909185e364bfda14
Source dataset
uspto-grants-2014_08
Patent number
US08815918B2

Reaction notes

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