Triethylamine → 4-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinolin-2-ylamine

HRID 1778161Notes

Reaction equation

HRID 1778161 reaction equation
C(N(CC)CC)C.CC1(C)C(C)(C)OBO1.I[C:18]1[C:26]2[C:21](=[N:22][CH:23]=[CH:24][CH:25]=2)[N:20](C(OC(C)(C)C)=O)[CH:19]=1.Br[C:35]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[N:38]=[C:37]([NH2:45])[CH:36]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.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.CO>[NH:20]1[C:21]2=[N:22][CH:23]=[CH:24][CH:25]=[C:26]2[C:18]([C:35]2[C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[N:38]=[C:37]([NH2:45])[CH:36]=2)=[CH:19]1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 10796Cesium carbonateHCID 27347684,4,5,5-Tetramethyl[1,3,2]dioxaborolaneHCID 140674194-Bromoquinolin-2-amineHCID 23529164tert-Butyl 3-iodo-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

Product 1

HCID 590535894-(1H-pyrrolo[2,3-b]pyridin-3-yl)quinolin-2-ylamine

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

0.42 ml (3.00 mmol) of triethylamine and 0.22 ml (1.5 mmol) of 4,4,5,5-tetramethyl-1,3,2-dioxaborolane are added successively to a solution, kept under argon, of 35 mg (0.03 mmol) of tetrakis(triphenylphosphine)palladium and 344 mg (1.00 mmol) of tert-butyl 3-iodopyrrolo[2,3-b]pyridine-1-carboxylate in 5 ml of dioxane, and the mixture is stirred at 80° C. for 3 hours under argon. The reaction mixture is cooled to room temperature; 5 ml of methanol, 223 mg (1.0 mmol) of 4-bromoquinolin-2-amine and 823 mg (2.50 mmol) of caesium carbonate are added successively. The reaction mixture is stirred at 100° C. for 18 hours. The reaction mixture is cooled to room temperature, absorbed onto kieselguhr and chromatographed on a silica-gel column with dichloromethane/methanol/dilute aqueous ammonia as eluent: 4-(1H-pyrrolo-[2,3-b]pyridin-3-yl)quinolin-2-ylamine (“A1”) as pale-pink crystals; m.p. 244° C.; 1H-NMR (d6-DMSO, 500 MHz): δ [ppm]=6.45 (s, 2H), 6.88 (s, 1H), 7.10-7.15 (m, 1H), 7.16 (dd, J=7.9 Hz, J=4.7 Hz, 1H), 7.47-7.51 (m, 1H), 7.53-7.56 (m, 1H), 7.78-7.81 (m, 1H), 7.86 (d, J=2.2 Hz, 1H), 7.89 (dd, J=7.9 Hz, J=1.6 Hz, 1H), 8.34 (dd, J=4.7 Hz, J=1.6 Hz, 1H), 12.2 (bs, 1H).

Workup

  1. temperatureThe reaction mixture is cooled to room temperature
  2. stirringThe reaction mixture is stirred at 100° C. for 18 hours
  3. temperatureThe reaction mixture is cooled to room temperature
  4. customabsorbed onto kieselguhr
  5. customchromatographed on a silica-gel column with dichloromethane/methanol/dilute aqueous ammonia as eluent

Sources & evidence

ORD record
ord-ca929fc6cd5440ef81a766bf6e7ff99b
Source dataset
uspto-grants-2016_02
Patent number
US09266887B2

Reaction notes

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