Hydrochloric Acid → 2-[(R)-5-(6-methyl-pyrimidin-4-yl)-indan-1-yl]-2,7-diaza-spiro[3.5]nonane dihydrochloride

HRID 2205092Notes

Reaction equation

HRID 2205092 reaction equation
[CH3:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[C@H:13]([N:17]2[CH2:20][C:19]4([CH2:25][CH2:24][N:23](C(OC(C)(C)C)=O)[CH2:22][CH2:21]4)[CH2:18]2)[CH2:12][CH2:11]3)[CH:3]=1.[ClH:33]>CO.O1CCOCC1>[ClH:33].[ClH:33].[CH3:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[C@H:13]([N:17]2[CH2:20][C:19]4([CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)[CH2:18]2)[CH2:12][CH2:11]3)[CH:3]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 674086712-[(R)-5-(6-Methylpyrimidin-4-yl)-indan-1-yl]-2,7-diazaspiro[3.5]nonane-7-carboxylic acid tert-butyl ester

Product 1

HCID 674062952-[(R)-5-(6-methyl-pyrimidin-4-yl)-indan-1-yl]-2,7-diaza-spiro[3.5]nonane dihydrochlorideYield 99.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

(R)-tert-butyl 2-(5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate (72.6 g, 167 mmol) was suspended in methanol (363 mL) and 4M HCl in 1,4-dioxane (251 mL) was added. After stirring for 2 hours, the slurry was concentrated to dryness. The crude material was re-suspended in MeOH (500 mL) and concentrated (3×). The resulting solids were further dried under vacuum at 45° C. to afford the title compound (74.1 g, 99.9%). MS (ES+) 335.2 (M+H)+. 1H NMR (CD3OD) δ 2.16-2.23 (m, 5H), 2.59 (br s, 1H), 2.78-2.80 (m, 3H), 3.12 (br s, 1H), 3.19-3.24 (m, 4H), 3.37-3.49 (m, 1H), 4.14-4.23 (m, 3H), 4.49 (br s, 1H), 5.11 (br s, 1H), 7.84 (d, 1H), 8.30-8.34 (m, 2H), 8.46 (s, 1H), 9.36 (s, 1H).

Workup

  1. concentrationthe slurry was concentrated to dryness
  2. concentrationconcentrated (3×)
  3. customThe resulting solids were further dried under vacuum at 45° C.

Sources & evidence

ORD record
ord-3d1d439c236a45099e1e8ca668139509
Source dataset
uspto-grants-2016_06
Patent number
US09370516B2

Reaction notes

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