1-Pyrrolidinepropanamine → HCID 53372570, compound

HRID 515836Notes

Reaction equation

HRID 515836 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].[N:33]1([CH2:38][CH2:39][CH2:40][NH2:41])[CH2:37][CH2:36][CH2:35][CH2:34]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.[Cl-].[Na+].O.CCOC(C)=O>[C:1]([C:3]1[N:8]=[CH:7][C:6]([N:9]2[C:16](=[O:17])[C:12]3([CH2:13][CH2:14][CH2:15]3)[N:11]([C:18]3[CH:26]=[CH:25][C:21]([C:22]([NH:41][CH2:40][CH2:39][CH2:38][N:33]4[CH2:37][CH2:36][CH2:35][CH2:34]4)=[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]

Participants

8

Reactant 4

HCID 316701-PyrrolidinepropanamineHCID 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 53372570HCID 53372570, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

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, 550 mg, 1.18 mmol), 3-(pyrrolidin-1-yl)propan-1-amine (303 mg, 2.37 mmol), HATU (673 mg, 1.77 mmol), and DIEA (0.6 mL, 3.54 mmol) in DMF (25 mL) was stirred at room temperature overnight. Brine and EtOAc were added and the aqueous layer was extracted with EtOAc (4×), the organics were combined, dried over sodium sulfate, and evaporated to dryness. The residue was purified by column chromatography on silica gel eluting with 0 to 20% MeOH/DCM to afford 4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-fluoro-N-(3-(pyrrolidin-1-yl)propyl)benzamide as a pale orange solid. 1H NMR (300 MHz, DMSO-d6) δ 9.22 (d, 1H), 8.75 (d, 1H), 8.64 (t, 1H), 7.83 (t, 1H), 7.47 (dd, 1H), 7.38 (dd, 1H), 3.35 (m, 4H), 2.65-2.54 (m, 6H), 2.53-2.43 (m, 2H), 2.03-1.93 (m, 1H), 1.74 (m, 6H), 1.64-1.53 (m, 1H). LCMS [M+1]+ 575.1.

Workup

  1. extractionthe aqueous layer was extracted with EtOAc (4×)
  2. dry with materialdried over sodium sulfate
  3. customevaporated to dryness
  4. customThe residue was purified by column chromatography on silica gel eluting with 0 to 20% MeOH/DCM

Sources & evidence

ORD record
ord-ad9da3e9070f41a6bc1d43fab4ec3aa5
Source dataset
uspto-grants-2015_08
Patent number
US09108944B2

Reaction notes

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