2-Fluoroethylamine → 2-(2-(4-(1-(2-fluoroethylamino)ethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide

HRID 1162765Notes

Reaction equation

[F:1][CH2:2][CH2:3][NH2:4].[C:5]([C:8]1[C:9]([C:29]([F:32])([F:31])[F:30])=[N:10][N:11]([CH2:13][C:14]([NH:16][C:17]2[S:21][C:20]3[CH2:22][CH2:23][CH2:24][CH2:25][C:19]=3[C:18]=2[C:26]([NH2:28])=[O:27])=[O:15])[CH:12]=1)(=O)[CH3:6].C([BH3-])#N.[Na+]>CO.CC(O)=O>[F:1][CH2:2][CH2:3][NH:4][CH:5]([C:8]1[C:9]([C:29]([F:31])([F:32])[F:30])=[N:10][N:11]([CH2:13][C:14]([NH:16][C:17]2[S:21][C:20]3[CH2:22][CH2:23][CH2:24][CH2:25][C:19]=3[C:18]=2[C:26]([NH2:28])=[O:27])=[O:15])[CH:12]=1)[CH3:6]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 2-fluoroethanamine (107 mg, 1.689 mmol) in MeOH (1.5 mL), AcOH was added until the pH reached 5. 2-(2-(4-acetyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (50 mg, 0.121 mmol) was added before the addition of sodium cyanoborohydride (7.58 mg, 0.121 mmol). The reaction was heated by microwave irradiation to 100° C. for 20 min. The reaction mixture was filtered before purification by preparative reverse phase HPLC. The product fractions were acidified to pH 4 before applying to a strong cation exchange cartridge (500 mg). The cartridge was washed with DCM/MeOH (1:1) before eluting the product with 2M NH3 in MeOH. The solvent was removed in vacuo to give the title compound (2.9 mg, 0.006 mmol, 5%).

Workup

filtrationThe reaction mixture was filtered before purification by preparative reverse phase HPLC
washThe cartridge was washed with DCM/MeOH (1:1)
washbefore eluting the product with 2M NH3 in MeOH
customThe solvent was removed in vacuo

Sources & evidence

ORD record: ord-0024ff8f993145bcb30ecedd1914ba2f
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07820707B2

Reaction notes

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