1,4-Dioxane hydrochloride → (2S)-2-aminomethyl-3-(4-chlorophenyl)-1-[4-(5-thiophen-2-yl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-propan-1-one dihydrochloride

HRID 1192362Notes

Reaction equation

HRID 1192362 reaction equation
C([C@:8]([CH2:39][NH2:40])([CH2:31][C:32]1[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=1)[C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[C:18]3[C:25]([C:26]4[S:27][CH:28]=[CH:29][CH:30]=4)=[CH:24][NH:23][C:19]=3[N:20]=[CH:21][N:22]=2)[CH2:13][CH2:12]1)=[O:10])(OC(C)(C)C)=O.[ClH:41].O1CCOCC1>O1CCOCC1>[ClH:38].[ClH:41].[NH2:40][CH2:39][C@H:8]([CH2:31][C:32]1[CH:33]=[CH:34][C:35]([Cl:38])=[CH:36][CH:37]=1)[C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[C:18]3[C:25]([C:26]4[S:27][CH:28]=[CH:29][CH:30]=4)=[CH:24][NH:23][C:19]=3[N:20]=[CH:21][N:22]=2)[CH2:13][CH2:12]1)=[O:10]

Participants

4

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 86598733(2S)-2-Boc-aminomethyl-3-(4-chlorophenyl)-1-[4-(5-thiophen-2-yl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-pip-erazin-1-yl]-propan-1-one

Product 1

HCID 67539010(2S)-2-aminomethyl-3-(4-chlorophenyl)-1-[4-(5-thiophen-2-yl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-propan-1-one dihydrochlorideYield 67%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of (2S)-2-Boc-aminomethyl-3-(4-chlorophenyl)-1-[4-(5-thiophen-2-yl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-pip-erazin-1-yl]-propan-1-one in 1.5 mL dioxane was added 1.5 mL 4M HCl/dioxane. The resulting suspension was stirred at room temperature 16 hours, after which it was concentrated to dryness. The solids were dissolved in minimal MeOH, and the product was triturated by the addition of ether. The solids were isolated by filtration through a fritted funnel with nitrogen pressure, rinsed with ether, and dried in vacuo to give (2S)-2-aminomethyl-3-(4-chlorophenyl)-1-[4-(5-thiophen-2-yl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-propan-1-one dihydrochloride (37 mg, 67%) a pale yellow powder. 1H NMR (D2O, 400 MHz) δ 8.18 (1H, s), 7.41 (1H, d, J 5.4 Hz), 7.30 (1H, s), 7.19 (2H, d, J 8.6 Hz), 7.06 (1H, dd, J 5.0 and 3.5 Hz), 7.01 (2H, d, J 8.0 Hz), 6.88 (1H, d, J 3.5 Hz), 3.47-3.14 (5H, m), 3.08-3.00 (3H, m), 2.86-2.77 (3H, m), 2.59 (1H, t, J 12.0 Hz), 2.13-2.06 (1H, m). LCMS (APCI+) m/z 481 [M+H]+; Rt: 1.87 min.

Workup

  1. concentrationafter which it was concentrated to dryness
  2. dissolutionThe solids were dissolved in minimal MeOH
  3. customthe product was triturated by the addition of ether
  4. customThe solids were isolated by filtration through a fritted funnel with nitrogen pressure
  5. washrinsed with ether
  6. customdried in vacuo

Sources & evidence

ORD record
ord-aef514065ac74f1cbf0e6696f78c7261
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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