Lithium Chloride → 5-(3-(quinolin-3-yl)-1H-indol-5-yl)thiazol-2-amine

HRID 634148

Reaction equation

HRID 634148 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7](C(OC(C)(C)C)=O)[CH:6]=[C:5]2[C:18]1[CH:19]=[N:20][C:21]2[C:26]([CH:27]=1)=[CH:25][CH:24]=[CH:23][CH:22]=2.[Cl-].[Li+].C([Sn](CCCC)(CCCC)[C:35]1[S:39][C:38]([NH:40]C(=O)OC(C)(C)C)=[N:37][CH:36]=1)CCC>CN(C=O)C.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>[N:20]1[C:21]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:27]=[C:18]([C:5]2[C:4]3[C:8](=[CH:9][CH:10]=[C:2]([C:35]4[S:39][C:38]([NH2:40])=[N:37][CH:36]=4)[CH:3]=3)[NH:7][CH:6]=2)[CH:19]=1

Participants

6

Reactant 3

HCID 433294Lithium ChlorideHCID 2763269tert-butyl N-(5-(tributylstannyl)-1,3-thiazol-2-yl)carbamateHCID 68327989tert-butyl 5-bromo-3-(quinolin-3-yl)-1H-indole-1-carboxylate

Product 1

HCID 867250985-(3-(quinolin-3-yl)-1H-indol-5-yl)thiazol-2-amine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
100 °C

Procedure

A mixture of tert-butyl 5-bromo-3-(quinolin-3-yl)-1H-indole-1-carboxylate (104 mg, 0.246 mmol), Pd(PPh3)4 (14 mg, 0.012 mmol), Lithium chloride (83 mg, 1.965 mmol) and DMF (2.0 ml, 0.246 mmol) in a microwave reaction vessel was sealed and heated at 100° C. for 5 min. A solution of tert-butyl 5-(tributylstannyl)thiazol-2-ylcarbamate (240 mg, 0.491 mmol) in DMF (1.0 mL) was then added and the reaction was heated at 100° C. for additional 17 h. The mixture was filtered through a pad of Celite and the filtrate was evaporated to dryness. The above crude product was dissolved in DCM (0.5 mL) followed by the addition of TFA (0.5 mL). The reaction was stirred at RT for 1 h then evaporated in vacuo to dryness. The residue was purified by silica gel chromatography to 5-(3-(quinolin-3-yl)-1H-indol-5-yl)thiazol-2-amine (6.7 mg, 8.0%) as a yellow solid. MS (ESI, pos. ion) m/z: 343 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 6.98 (s, 2H), 7.32 (d, J=9.0 Hz, 1H), 7.38 (s, 1H), 7.48 (d, J=8.5 Hz, 1H), 7.62 (t, J=7.5 Hz, 1H), 7.70 (t, J=7.3 Hz, 1H), 7.98 (s, 1H), 8.00-8.05 (m, 2H), 8.10 (d, J=8.0 Hz, 1H), 8.62 (s, 1H), 9.29 (d, J=2.0 Hz, 1H), 11.65 (s, 1H).

Workup

  1. customin a microwave reaction vessel
  2. customwas sealed
  3. temperaturethe reaction was heated at 100° C. for additional 17 h
  4. filtrationThe mixture was filtered through a pad of Celite
  5. customthe filtrate was evaporated to dryness
  6. dissolutionThe above crude product was dissolved in DCM (0.5 mL)
  7. additionfollowed by the addition of TFA (0.5 mL)
  8. customthen evaporated in vacuo to dryness
  9. customThe residue was purified by silica gel chromatography to 5-(3-(quinolin-3-yl)-1H-indol-5-yl)thiazol-2-amine (6.7 mg, 8.0%) as a yellow solid

Sources & evidence

ORD record
ord-4435b4f2a0af454bad0a062953c1a040
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Linked notes

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