HCID 68614256, compound → HCID 10361910, compound

HRID 1592883Notes

Reaction equation

Br.C1C2(CCN=C(N)N2)CCC1.[OH:13][C@@H:14]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[CH2:15][N:16]1[C:21]2([CH2:25][CH2:24]CC2)[CH2:20][CH2:19][N:18]2[C:26](=[O:36])[CH:27]=[C:28]([C:30]3[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=3)[N:29]=[C:17]12>>[O:13]=[C:14]([C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1)[CH2:15][N:16]1[C:21]2([CH2:24][CH2:25]2)[CH2:20][CH2:19][N:18]2[C:26](=[O:36])[CH:27]=[C:28]([C:30]3[CH:31]=[CH:32][N:33]=[CH:34][CH:35]=3)[N:29]=[C:17]12

Participants

Reactant 2

HCID 68614256HCID 68614256, compound

HCID 68615690HCID 68615690, compound

Product 1

HCID 10361910HCID 10361910, compound

Procedure

A solution of 15.91 g (0.15 mol) of cyclopentylideneacetonitrile in 170 ml of an aqueous ammonia solution (29%) and 57 ml of methanol was heated at 100° C. in a sealed tube for 24 h. The reaction mixture was concentrated, and the residue was chromatographed on silica gel eluting with a mixture of dichloromethane/methanol in the proportions 90/10 to afford 12.15 g of the product as a colorless oil. 3.2 Tert-butyl 1-(cyanomethyl)cyclopentylcarbamate The product was obtained by analogy with the method described in step 1.2 and using (1-aminocyclopentyl)acetonitrile. The compound was used as such in the next step. 3.3 Tert-butyl 1-(2-aminoethyl)cyclopentylcarbamate To a suspension of 8.48 g (223.63 mmol) of lithium aluminum hydride in 687 ml of diethyl ether at 0° C. was added dropwise 16.7 g (74.54 mmol) of tert-butyl 1-(cyanomethyl)cyclopentylcarbamate dissolved in 344 ml of diethyl ether. The resulting mixture was stirred at 0° C. under nitrogen atmosphere for 1 h. The reaction mixture was diluted with 100 ml of diethyl ether at 0° C. and treated with excess of a saturated aqueous solution of sodium sulfate. Further solid sodium sulfate was added and the organic phase was filtered to remove salts. The solvent was evaporated to dryness to give 13.83 g of product as an oil. 3.4 1-(2-Aminoethyl)cyclopentanamine hydrobromide (1:2) The product was obtained by analogy with the method described in step 1.6 and using tert-butyl 1-(2-aminoethyl)cyclopentylcarbamate. The compound was used as such in the next step. Mp: 194-196° C. 3.5 6,8-Diazaspiro[4.5]dec-7-en-7amine hydrobromide (1:1) The product was obtained by analogy with the method described in step 1.7 and using 1-(2-aminoethyl)cyclopentanamine hydrobromide (1:2). The compound was used as such in the next step. 3.6 8′-Pyridinyl-4-yl-3′,4′-dihydrospiro[cyclopentane-1,2′-pyrimido[1,2-a]pyrimidin]-6′(1′H)-one The product was obtained by analogy with the method described in step 1.8 and using 6,8-diazaspiro[4.5]dec-7-en-7amine hydrobromide (1:1). The compound was used as such in the next step. Mp: 241-243° C. 3.7 1′-[(2S)-2-Hydroxy-2-phenylethyl]-8′-pyridin-4-yl-3′,4′-dihydrospiro[cyclopentane-1,2′-pyrimido[1,2-a]pyrimidin]-6′(1′H)-one.(1:1) (hydrochloride) The product was obtained by analogy with the method described in step 1.9 and using 8′-pyridinyl-4-yl-3′,4′-dihydrospiro[cyclopentane-1,2′-pyrimido[1,2-a]-pyrimidin]-6′(1′H)-one.

Sources & evidence

ORD record: ord-58e2d9812e124dc28f4dc476850cf86f
Source dataset: uspto-grants-2007_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07294632B2

Reaction notes

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