Sodium hydride → 6-Benzyloxy-4-(4-fluoro-1H-pyrrolo[2,3-b]pyridin-5-yloxy)-5-methyl-pyrrolo[2,1-f][1,2,4]triazine

HRID 1064228Notes

Reaction equation

HRID 1064228 reaction equation
[F:1][C:2]1[C:7]([OH:8])=[CH:6][N:5]=[C:4]2[NH:9][CH:10]=[CH:11][C:3]=12.[H-].[Na+].[CH2:14]([O:21][C:22]1[C:23]([CH3:32])=[C:24]2[N:29]([CH:30]=1)[N:28]=[CH:27][N:26]=[C:25]2Cl)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[Cl-].[NH4+]>CN(C=O)C>[CH2:14]([O:21][C:22]1[C:23]([CH3:32])=[C:24]2[N:29]([CH:30]=1)[N:28]=[CH:27][N:26]=[C:25]2[O:8][C:7]1[C:2]([F:1])=[C:3]2[CH:11]=[CH:10][NH:9][C:4]2=[N:5][CH:6]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 116376306-Benzyloxy-4-chloro-5-methylpyrrolo[2,1-f][1,2,4]triazineHCID 222736554-Fluoro-1H-pyrrolo[2,3-B]pyridin-5-OL

Product 1

HCID 222736636-Benzyloxy-4-(4-fluoro-1H-pyrrolo[2,3-b]pyridin-5-yloxy)-5-methyl-pyrrolo[2,1-f][1,2,4]triazineYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-fluoro-1H-pyrrolo[2,3-b]pyridin-5-ol (53.5 mg, 0.35 mmol) in DMF (2 mL) at −78° C., sodium hydride (60% in oil, 14 mg, 0.35 mmol) was added and the mixture was warmed to 0° C. After 30 minutes, the flask was cooled to −78° C., 6-benzyloxy-4-chloro-5-methyl-pyrrolo[2,1-f][1,2,4]triazine (80 mg, 0.29 mmol) was added and the mixture was allowed to reach RT over 30 min. A solution of saturated ammonium chloride was added, the solution was extracted with ethyl acetate (3×15 mL), combined organic layers were washed with water (30 mL), brine (30 mL), dried, and concentrated in vacuo. The crude material was purified by trituration with acetonitrile to give the title compound (90 mg, 80%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 12.17 (1H, s), 8.30 (1H, d, J=9.6 Hz), 8.00 (1H, s), 7.94 (1H, s), 7.61 (1H, t, J=3.0 Hz), 7.49 (2H, d, J=7.1 Hz), 7.41 (2H, t, J=7.1 Hz), 7.34 (1H, t, J=7.3 Hz), 6.59 (1H, dd, J=2.0, 3.5 Hz), 5.16 (2H, s), 2.43 (3H, s). LC/MS; (M+H)+=m/z 390.

Workup

  1. temperaturethe flask was cooled to −78° C.
  2. waitto reach RT over 30 min
  3. extractionthe solution was extracted with ethyl acetate (3×15 mL)
  4. washwere washed with water (30 mL), brine (30 mL)
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by trituration with acetonitrile

Sources & evidence

ORD record
ord-8537564f09f04ed0b6786d5a771cfa14
Source dataset
uspto-grants-2005_11
Patent number
US06969717B2

Reaction notes

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