Benzylamine → HCID 53372693, compound

HRID 515834Notes

Reaction equation

HRID 515834 reaction equation
[C:1]([C:3]1[N:8]=[CH:7][C:6]([N:9]2[C:16](=[O:17])[C:12]3([CH2:15][CH2:14][CH2:13]3)[N:11]([C:18]3[CH:26]=[CH:25][C:21]([C:22](O)=[O:23])=[C:20]([F:27])[CH:19]=3)[C:10]2=[S:28])=[CH:5][C:4]=1[C:29]([F:32])([F:31])[F:30])#[N:2].[CH2:33]([NH2:40])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:33]([NH:40][C:22](=[O:23])[C:21]1[CH:25]=[CH:26][C:18]([N:11]2[C:10](=[S:28])[N:9]([C:6]3[CH:7]=[N:8][C:3]([C:1]#[N:2])=[C:4]([C:29]([F:31])([F:30])[F:32])[CH:5]=3)[C:16](=[O:17])[C:12]32[CH2:15][CH2:14][CH2:13]3)=[CH:19][C:20]=1[F:27])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

6

Reactant 4

HCID 7504BenzylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86683488Apalutamide Acid Impurity2×

Product 1

HCID 53372693HCID 53372693, compoundYield 65.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-fluorobenzoic acid (Compound 224, 68 mg, 0.14 mmol), benzylamine (22 mg, 0.21 mmol), HATU (70 mg, 0.18 mmol), and DIEA (40 μL, 0.21 mmol) in DMF (3 mL) was stirred at room temperature for 3 h. The crude reaction mixture was purified by reverse phase HPLC (acetonitrile/water:TFA) to afford 51 mg of N-benzyl-4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-fluorobenzamide as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 9.22 (d, 1H), 9.12 (t, 1H), 8.75 (d, 1H), 7.87 (t, 1H), 7.49 (dd, 1H), 7.40 (dd, 1H), 7.37-7.31 (m, 4H), 7.29-7.24 (m, 1H), 4.51 (d, 1H), 2.69-2.63 (m, 2H), 2.55-2.44 (m, 2H), 2.03-1.94 (m, 1H), 1.62-1.56 (m, 1H). LCMS [M+1]+ 554.5.

Workup

  1. customThe crude reaction mixture
  2. customwas purified by reverse phase HPLC (acetonitrile/water:TFA)

Sources & evidence

ORD record
ord-7408564f594c4f938caf959bb007e40f
Source dataset
uspto-grants-2015_08
Patent number
US09108944B2

Reaction notes

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