Potassium Carbonate → 4-(6-(5-(5-bromo-1,3,4-thiadiazol-2-yl)-1H-indol-3-yl)pyridin-2-yl)morpholine

HRID 634165Notes

Reaction equation

HRID 634165 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[N:12]=[C:11]([C:13]3[C:21]4[C:16](=[CH:17][CH:18]=[C:19](B5OC(C)(C)C(C)(C)O5)[CH:20]=4)[N:15](C(OC(C)(C)C)=O)[CH:14]=3)[CH:10]=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.[Br:38][C:39]1[S:40][C:41](Br)=[N:42][N:43]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C(Cl)Cl.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>[Br:38][C:39]1[S:40][C:41]([C:19]2[CH:20]=[C:21]3[C:16](=[CH:17][CH:18]=2)[NH:15][CH:14]=[C:13]3[C:11]2[N:12]=[C:7]([N:4]3[CH2:5][CH2:6][O:1][CH2:2][CH2:3]3)[CH:8]=[CH:9][CH:10]=2)=[N:42][N:43]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 30925302,5-Dibromo-1,3,4-thiadiazoleHCID 68328848tert-butyl 3-(6-morpholinopyridin-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate

Product 1

HCID 683286874-(6-(5-(5-bromo-1,3,4-thiadiazol-2-yl)-1H-indol-3-yl)pyridin-2-yl)morpholineYield 16.45%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

A glass microwave reaction vessel was charged with tert-butyl 3-(6-morpholinopyridin-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate (250 mg, 0.495 mmol) and 2,5-dibromo-1,3,4-thiadiazole (133 mg, 0.544 mmol) in p-dioxane/H2O (4:1, 4.5 mL) followed by potassium carbonate (205 mg, 1.484 mmol) and Pd(PPh3)4 (28.6 mg, 0.025 mmol). The reaction was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 100° C. for 75 min. The mixture was diluted with DCM, washed with H2O, dried, filtered and concentrated. The residue was purified with silica gel chromatography (eluting with 2-10% EtOAc in DCM) to give 4-(6-(5-(5-bromo-1,3,4-thiadiazol-2-yl)-1H-indol-3-yl)pyridin-2-yl)morpholine (36.0 mg, 0.081 mmol, 16.45%) as a yellow solid. MS (ESI, pos. ion) 442 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.85 (1H, br. s.), 9.11 (1H, d, J=1.6 Hz), 8.19 (1H, d, J=2.5 Hz), 7.80 (1H, dd, J=8.6, 1.8 Hz), 7.56-7.64 (2H, m), 7.24 (1H, d, J=7.4 Hz), 6.67 (1H, d, J=8.4 Hz), 3.79-3.86 (4H, m), 3.58-3.65 (4H, m).

Workup

  1. customA glass microwave reaction vessel
  2. washwashed with H2O
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified with silica gel chromatography (eluting with 2-10% EtOAc in DCM)

Sources & evidence

ORD record
ord-97468481d43c457b8ea9162af96f81f1
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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