Potassium Phosphate, Tribasic → 5-(3-(6-(1-pyrrolidinyl)-2-pyridinyl)-1H-indol-5-yl)-1,3,4-thiadiazol-2-amine

HRID 634134Notes

Reaction equation

HRID 634134 reaction equation
[N:1]1([C:6]2[CH:11]=[CH:10][CH:9]=[C:8](B3OC(C)(C)C(C)(C)O3)[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.I[C:22]1[C:30]2[C:25](=[CH:26][CH:27]=[C:28]([C:31]3[S:35][C:34]([NH2:36])=[N:33][N:32]=3)[CH:29]=2)[N:24](S(C2C=CC(C)=CC=2)(=O)=O)[CH:23]=1.CC(N)CC1C=CC=CC=1.OP(O)(O)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CC(O)C.O>[N:1]1([C:6]2[N:7]=[C:8]([C:22]3[C:30]4[C:25](=[CH:26][CH:27]=[C:28]([C:31]5[S:35][C:34]([NH2:36])=[N:33][N:32]=5)[CH:29]=4)[NH:24][CH:23]=3)[CH:9]=[CH:10][CH:11]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 62885Benzeneethanamine, alpha-methyl-, phosphate (1:1)HCID 457857172-(Pyrrolidin-1-YL)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)pyridineHCID 68328527HCID 68328527, compound

Product 1

HCID 683283905-(3-(6-(1-pyrrolidinyl)-2-pyridinyl)-1H-indol-5-yl)-1,3,4-thiadiazol-2-amineYield 8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
100 °C

Procedure

A glass microwave reaction vessel was charged with 2-(pyrrolidin-1-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (46 mg, 0.17 mmol, CombiPhos Catalysts, Inc.) and 5-(3-iodo-1-tosyl-1H-indol-5-yl)-1,3,4-thiadiazol-2-amine (060 g, 0.12 mmol) in 66% IPA in H2O (1 mL) followed by Amphos (4 mg, 6 μmol), potassium phosphate (0.077 g, 0.36 mmol). The mixture was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 100° C. for 10 min. The aqueous layer was removed and the resulting mixture was concentrated in vacuo and purified by preparative HPLC. The product was dissolved in p-dioxane (1 mL) and aq. NaOH (1 M, 0.1 mL) was added. The solution was heated in a microwave at 100° C. for 10 min, and purified by preparative HPLC to give 5-(3-(6-(1-pyrrolidinyl)-2-pyridinyl)-1H-indol-5-yl)-1,3,4-thiadiazol-2-amine (3 mg, 8%). MS (ESI, pos. ion) m/z: 364 (M+1). 1H NMR (400 MHz, CD3OD) δ ppm 8.23 (1H, s), 8.00 (1H, s), 7.91 (1H, dd, J=9.0, 7.6 Hz), 7.65 (1H, d, J=8.6 Hz), 7.58 (1H, d, J=8.6 Hz), 7.09 (1H, d, J=7.2 Hz), 6.85 (1H, d, J=9.0 Hz), 3.60-3.68 (4H, m), 2.06-2.14 (4H, m).

Workup

  1. customA glass microwave reaction vessel
  2. customThe aqueous layer was removed
  3. concentrationthe resulting mixture was concentrated in vacuo
  4. custompurified by preparative HPLC
  5. dissolutionThe product was dissolved in p-dioxane (1 mL)
  6. additionaq. NaOH (1 M, 0.1 mL) was added
  7. temperatureThe solution was heated in a microwave at 100° C. for 10 min
  8. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-e8894fc6ebd64df8b9a8a227b5fc2fdf
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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