tert-Butyl (3-aminopropyl)carbamate → N-(5-(3-(2-fluorophenyl)-1H-indol-5-yl)-1,3,4-thiadiazol-2-yl)-1,3-propanediamine

HRID 634127Notes

Reaction equation

HRID 634127 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]3[S:18]C(S(C)(=O)=O)=[N:20][N:21]=3)[CH:15]=2)[N:10](S(C2C=CC(C)=CC=2)(=O)=O)[CH:9]=1.[NH2:36][CH2:37][CH2:38][CH2:39][NH:40][C:41](=O)OC(C)(C)C>O1CCOCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]3[S:18][C:41]([NH:40][CH2:39][CH2:38][CH2:37][NH2:36])=[N:20][N:21]=3)[CH:15]=2)[NH:10][CH:9]=1

Participants

4

Reactant 2

HCID 2735700tert-Butyl (3-aminopropyl)carbamateHCID 683279772-(3-(2-fluorophenyl)-1-tosyl-1H-indol-5-yl)-5-(methylsulfonyl)-1,3,4-thiadiazole

Product 1

HCID 68328011N-(5-(3-(2-fluorophenyl)-1H-indol-5-yl)-1,3,4-thiadiazol-2-yl)-1,3-propanediamineYield 87.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 2-(3-(2-fluorophenyl)-1-tosyl-1H-indol-5-yl)-5-(methylsulfonyl)-1,3,4-thiadiazole (0.053 g, 0.10 mmol) in p-dioxane (1 mL) was added tert-butyl 3-aminopropylcarbamate (88 mg, 0.50 mmol, Aldrich), and the reaction was heated at 90° C. for 8 h. The residue was then purified with RP-HPLC. The purified material was dissolved in dioxane (1 mL) and aq. NaOH (1M, 0.1 mL) was added. The solution was heated in a microwave at 120° C. for 10 min. The solution was concentrated under reduced pressure and the resulting oil was stirred with 4M HCl/dioxane for 30 min, then evaporated under reduced pressure. The residue was purified by preparative HPLC to give N-(5-(3-(2-fluorophenyl)-1H-indol-5-yl)-1,3,4-thiadiazol-2-yl)-1,3-propanediamine (32 mg, 61.4%). MS (ESI, pos. ion) m/z: 368 (M+1). 1H NMR (400 MHz, CD3OD) δ ppm 8.10 (1H, s), 7.66-7.72 (1H, m), 7.62-7.66 (1H, m), 7.59 (1H, d, J=1.6 Hz), 7.53-7.57 (1H, m), 7.17-7.35 (3H, m), 3.57 (2H, t, J=6.7 Hz), 3.03-3.10 (2H, m), 2.04-2.11 (2H, m).

Workup

  1. customThe residue was then purified with RP-HPLC
  2. dissolutionThe purified material was dissolved in dioxane (1 mL)
  3. additionaq. NaOH (1M, 0.1 mL) was added
  4. temperatureThe solution was heated in a microwave at 120° C. for 10 min
  5. concentrationThe solution was concentrated under reduced pressure
  6. customevaporated under reduced pressure
  7. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-e9f0146b50104bf88195ece8cf9686c2
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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