Ammonia → (4-Bromo-2-chloro-phenyl)-[4-fluoro-6-(3H-imidazol-4-yl)-1H-benzoimidazol-5-yl]-amine

HRID 1925860Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:23]([CH:24]3O[CH:27]=[N:26][CH:25]3S(C3C=CC(C)=CC=3)(=O)=O)=[CH:22][C:12]3[N:13](CCS(C)(=O)=O)[CH:14]=[N:15][C:11]=3[C:10]=2[F:39])=[C:4]([Cl:40])[CH:3]=1.[NH3:41]>CO>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:23]([C:24]3[NH:41][CH:27]=[N:26][CH:25]=3)=[CH:22][C:12]3[NH:13][CH:14]=[N:15][C:11]=3[C:10]=2[F:39])=[C:4]([Cl:40])[CH:3]=1

Participants

Conditions

Temperature: 90 °C

Procedure

(4-Bromo-2-chloro-phenyl)-{4-fluoro-1-(2-methanesulfonyl-ethyl)-6-[4-(toluene-4-sulfonyl)-4,5-dihydro-oxazol-5-yl]-1H-benzoimidazol-5-yl}-amine 10bb (0.072 g, 0.107 mmol) is treated with 2.4 mL of a 2.0 M NH3 in MeOH solution in a sealed pressure tube. The reaction mixture is then heated to 90° C. with stirring for 20 hours and furthered stirred at room temperature for 3 days. The reaction mixture is transferred to a round bottom flask and concentrated under reduced pressure. Purification by flash column chromatography, twice, eluted with 10:1 methylene chloride:MeOH, followed by successive triturations with methylene chloride and then diethyl ether provides 3 mg (7%) desired product: LC/MS ESI (+) m/z 408, 406 (M+Br pattern) detected; 1H NMR (400 MHz, MeOH-d4) δ 8.23 (s, 1H), 7.87 (s, 1H), 7.74 (s, 1H), 7.46 (m, 1H), 7.32 (d, 1H), 7.05 (m, 1H), 6.20 (dd, 1H).

Workup

stirringfurthered stirred at room temperature for 3 days
customThe reaction mixture is transferred to a round bottom flask
concentrationconcentrated under reduced pressure
customPurification by flash column chromatography
washtwice, eluted with 10:1 methylene chloride

Sources & evidence

ORD record: ord-5850c81a78c24665afcac5c450b07b22
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08178693B2

Reaction notes

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