Tert-Butyl nitrite → HCID 57990021, compound

HRID 1961968Notes

Reaction equation

HRID 1961968 reaction equation
N[C:2]1[S:3][C:4]([C:25]2[CH:30]=[CH:29][N:28]=[C:27]([Cl:31])[N:26]=2)=[C:5]([C:7]2[CH:8]=[C:9]([NH:13][S:14]([C:17]3[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=3[F:24])(=[O:16])=[O:15])[CH:10]=[CH:11][CH:12]=2)[N:6]=1.C(ON=O)(C)(C)C>C1COCC1.CCOC(C)=O>[Cl:31][C:27]1[N:26]=[C:25]([C:4]2[S:3][CH:2]=[N:6][C:5]=2[C:7]2[CH:8]=[C:9]([NH:13][S:14]([C:17]3[C:18]([F:24])=[CH:19][CH:20]=[CH:21][C:22]=3[F:23])(=[O:16])=[O:15])[CH:10]=[CH:11][CH:12]=2)[CH:30]=[CH:29][N:28]=1

Participants

5

Reactant 2

HCID 10906Tert-Butyl nitrite2×HCID 57989827HCID 57989827, compound

Product 1

HCID 57990021HCID 57990021, compoundYield 68.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To N-{3-[2-amino-5-(2-chloro-4-pyrimidinyl)-1,3-thiazol-4-yl]phenyl}-2,6-difluorobenzene sulfonamide (0.8 g, 1.67 mmol) in 10 mL THF was added t-butylnitrite (0.4 mL, 4 mmol) by syringe. The mixture stirred at rt for 1 h. More t-butylnitrite (0.2 mL, 2 mmol) was added and the mixture heated to 80° C. for 1 h. The mixture was cooled, diluted with 100 mL EtOAc, washed with 20 mL water, filtered through Whatman 1 PS (phase separating) paper and concentrated under vacuum. The crude product was then purified by flash chromatography to give the title compound of Step B (0.53 g, 1.14 mmol, 65% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.07 (s, 1H), 9.37 (s, 1H), 8.55 (d, J=5.3 Hz, 1H), 7.65-7.75 (m, 1H), 7.40 (t, J=8.0 Hz, 1H), 7.23-7.32 (m, 5H), 7.03 (d, J=5.3 Hz, 1H).

Workup

  1. temperaturethe mixture heated to 80° C. for 1 h
  2. temperatureThe mixture was cooled
  3. washwashed with 20 mL water
  4. filtrationfiltered through Whatman 1 PS (phase separating) paper
  5. concentrationconcentrated under vacuum
  6. customThe crude product was then purified by flash chromatography

Sources & evidence

ORD record
ord-b37f033740964d8c82dcdad1da7c47ef
Source dataset
uspto-grants-2013_04
Patent number
US08415345B2

Reaction notes

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