Cesium fluoride → HCID 86661693, compound

HRID 1262287Notes

Reaction equation

HRID 1262287 reaction equation
[NH2:1][C:2]1[CH:20]=[CH:19][C:5]2[CH2:6][CH2:7][CH:8]([NH:12][C:13](=[O:18])[C:14]([F:17])([F:16])[F:15])[C:9](=[O:11])[NH:10][C:4]=2[CH:3]=1.CS([C:24]1[N:29]=[CH:28][C:27]2=[CH:30][CH:31]=[C:32]([C:33]3[CH:38]=[CH:37][C:36]([S:39]([CH3:42])(=[O:41])=[O:40])=[CH:35][CH:34]=3)[N:26]2[N:25]=1)=O.[F-].[Cs+].C(N(CC)C(C)C)(C)C>C(O)(C)(C)C>[F:16][C:14]([F:17])([F:15])[C:13]([NH:12][CH:8]1[C:9](=[O:11])[NH:10][C:4]2[CH:3]=[C:2]([NH:1][C:24]3[N:29]=[CH:28][C:27]4=[CH:30][CH:31]=[C:32]([C:33]5[CH:34]=[CH:35][C:36]([S:39]([CH3:42])(=[O:41])=[O:40])=[CH:37][CH:38]=5)[N:26]4[N:25]=3)[CH:20]=[CH:19][C:5]=2[CH2:6][CH2:7]1)=[O:18]

Participants

6

Reactant 4

HCID 25953Cesium fluorideHCID 81531DiisopropylethylamineHCID 667110462-(Methylsulfinyl)-7-(4-(methylsulfonyl)phenyl)pyrrolo[2,1-f][1,2,4]triazineHCID 86661694HCID 86661694, compound

Product 1

HCID 86661693HCID 86661693, compoundYield 32.7%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
130 °C

Procedure

Into a 8-dram vial, N-(8-Amino-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl)-2,2,2-trifluoro-acetamide (39.4 mg, 0.137 mmol), 2-Methanesulfinyl-7-(4-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazine (105 mg, 0.313 mmol), Cesium fluoride (41.7 mg, 0.274 mmol), tert-Butyl alcohol (0.80 mL) and N,N-Diisopropylethylamine (0.0478 mL, 0.274 mmol) were added. The reaction mixture was heated at 130° C. overnight. HPLC suggested no starting material. The solvent was evaporated. The reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN. The collected fractions were lyophilized to give 2,2,2-Trifluoro-N-{8-[7-(4-methanesulfonyl-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-yl}-acetamide as a yellow solid (25 mg, 32%). LCMS (E/I+) 559.07 (M+H). NMR 1H (DMSO-d6)-9.96 (s, 1H0, 9.74 (s, 1H), 9.65 (bs, 1H), 9.08 (s, 1H), 8.46 (d, 2H, J=7.72 Hz), 8.04 (d, 2H, J=7.72 Hz), 7.59 (s, 1H), 7.54 (d, 1H, J=8.49 Hz), 7.35 (bs, 1H), 7.28 (d, 1H, J=7.72 Hz), 7.03 (d, 1H, J=4.62 Hz), 4.29 (bs, 1H), 3.22 (s, 3H), 2.63-2.72 (m, 2H), 2.24-2.35 (m, 2H).

Workup

  1. customThe solvent was evaporated
  2. customThe reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN

Sources & evidence

ORD record
ord-8e5e5ec174d945f59c02ae6008c9cb85
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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