2-Pyridineethanamine → HCID 53372571, compound

HRID 515835Notes

Reaction equation

HRID 515835 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]([OH:24])=O)=[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].[N:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[CH2:39][CH2:40][NH2:41].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>[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]([NH:41][CH2:40][CH2:39][C:34]4[CH:35]=[CH:36][CH:37]=[CH:38][N:33]=4)=[O:24])=[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]

Participants

6

Reactant 4

HCID 759192-PyridineethanamineHCID 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 53372571HCID 53372571, compoundYield 59.8%

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, 70 mg, 0.15 mmol), 2-(pyridin-2-yl)ethanamine (24 mg, 0.20 mmol), HATU (74 mg, 0.20 mmol), and DIEA (80 mL, 0.45 mmol) in DMF (3 mL) was stirred at room temperature overnight. The crude reaction mixture was purified by reverse phase HPLC (acetonitrile/water, 0.1% TFA). The fractions containing the desired compound were combined, acetonitrile was removed in vacuo, and the remaining aqueous layer was treated with a saturated solution of sodium bicarbonate. The aqueous layer was extracted with DCM (3×), the organics were combined, dried over sodium sulfate, and evaporated to dryness to afford 51 mg of 4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-fluoro-N-(2-(pyridin-2-yl)ethyl)benzamide as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 9.22 (d, 1H), 8.75 (d, 1H), 8.66 (t, 1H), 8.52 (d, 1H), 7.82-7.70 (m, 2H), 7.47-7.22 (m, 4H), 3.65 (q, 2H), 3.01 (t, 2H), 2.68-2.62 (m, 2H), 2.54-2.43 (m, 2H), 2.03-1.93 (m, 1H), 1.60-1.57 (m, 1H). LCMS [M+1]+ 569.5.

Workup

  1. customThe crude reaction mixture
  2. customwas purified by reverse phase HPLC (acetonitrile/water, 0.1% TFA)
  3. additionThe fractions containing the desired compound
  4. customacetonitrile was removed in vacuo
  5. additionthe remaining aqueous layer was treated with a saturated solution of sodium bicarbonate
  6. extractionThe aqueous layer was extracted with DCM (3×)
  7. dry with materialdried over sodium sulfate
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-b2f676d0ce134abf82c683802f32dbf3
Source dataset
uspto-grants-2015_08
Patent number
US09108944B2

Reaction notes

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