Tetrahydrofuran → HCID 178482364, compound

HRID 252656Notes

Reaction equation

HRID 252656 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([NH:10][C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[C:23]([C:24]5[CH:29]=[CH:28][N:27]=[C:26](S(C)=O)[N:25]=5)=[CH:22][CH:21]=[CH:20][N:19]=4)=[CH:13][N:12]=3)[NH:7][C:6]=2[C:33]=1[F:34].FC1C=CC2N=C(NC3C=CC(OC4C(C5C=CN=C(S(C)(=O)=O)N=5)=CC=CN=4)=CN=3)[NH:41][C:40]=2C=1F.C1COCC1>CN.CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([NH:10][C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[C:23]([C:24]5[CH:29]=[CH:28][N:27]=[C:26]([NH:41][CH3:40])[N:25]=5)=[CH:22][CH:21]=[CH:20][N:19]=4)=[CH:13][N:12]=3)[NH:7][C:6]=2[C:33]=1[F:34]

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 178504616HCID 178504616, compoundHCID 178504842HCID 178504842, compound

Product 1

HCID 178482364HCID 178482364, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6329MethylamineSolvent

Conditions

Temperature
70 °C

Procedure

The mixture of 6,7-difluoro-N-(5-(3-(2-(methylsulfinyl)pyrimidin-4-yl)pyridin-2-yloxy)pyridin-2-yl)-1H-benzo[d]imidazol-2-amine and 6,7-difluoro-N-(5-(3-(2-(methylsulfonyl)pyrimidin-4-yl)pyridin-2-yloxy)pyridin-2-yl)-1H-benzo[d]imidazol-2-amine (0.140 g, 0.28 mmol) in methylamine, 2.0 M solution in THF (2.1 ml, 4.2 mmol) was heated in a sealed tube to 70° C. After 4 h, the reaction was partitioned between EtOAc and 1 N NaOH, and the aqueous suspension was extracted 1×EtOAc, 3× dichloromethane, and the suspension was then filtered and rinsed with methanol. The solid material was combined with the combined organic layers adsorbed onto 2 g silica gel and purified with silica gel chromatography, eluting with 0-75% MC-90/10 MC/MeOH to give a white solid. The solid was sonicated in methanol and filtered, rinsing with Et2O. The resulting material was dried in vacuo to give 6,7-difluoro-N-(5-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)pyridin-2-yl)-1H-benzo[d]imidazol-2-amine as a white solid. MS m/z=447 [M+H]+. Calc'd for C22H16F2N8O: 446.4.

Workup

  1. customthe reaction was partitioned between EtOAc and 1 N NaOH
  2. extractionthe aqueous suspension was extracted 1×EtOAc, 3× dichloromethane
  3. filtrationthe suspension was then filtered
  4. washrinsed with methanol
  5. custompurified with silica gel chromatography
  6. washeluting with 0-75%
  7. custom/10 MC/MeOH to give a white solid
  8. filtrationfiltered
  9. washrinsing with Et2O
  10. customThe resulting material was dried in vacuo

Sources & evidence

ORD record
ord-6d15ce8e727241bf8cb931077ea4dc48
Source dataset
uspto-grants-2011_01
Patent number
US07868177B2

Reaction notes

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