L-Alaninol → HCID 59910456, compound

HRID 1280563Notes

Reaction equation

HRID 1280563 reaction equation
C(S([C:10]1[N:15]=[C:14]2[N:16]([CH:28]3[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]3)[C:17](=[O:27])[N:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[Cl:26])[CH2:19][C:13]2=[CH:12][N:11]=1)=O)C1C=CC=CC=1.[NH2:34][C@@H:35]([CH3:38])[CH2:36][OH:37].ClCCl.CO>COCCOC>[Cl:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[N:18]1[CH2:19][C:13]2[C:14](=[N:15][C:10]([NH:34][C@@H:35]([CH3:38])[CH2:36][OH:37])=[N:11][CH:12]=2)[N:16]([CH:28]2[CH2:29][CH2:30][NH:31][CH2:32][CH2:33]2)[C:17]1=[O:27]

Participants

5

Reactant 3

HCID 80307L-AlaninolHCID 18425472HCID 18425472, compoundHCID 21226129Dichloromethane methanol

Product 1

HCID 59910456HCID 59910456, compoundYield 63.3%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 7-benzylsulfinyl-3-(2-chlorophenyl)-1-(piperidin-4-yl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one (650 mg, 1.136 mmol) in 1,2-dimethoxyethane (0.5mL) was added (S)-(+)-2-amino-1-propanol (250 mg, 3.33 mmol). The reaction was warmed to 100° C. under argon for 2 hours. The reaction was placed directly on a flash silica column using 92:8-90:10 dichloromethane/methanol as eluant to give 300 mg of the (S)-3-(2-chlorophenyl)-7-(2-hydroxy-1-methylethylamino)-1-(piperidin-4-yl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one, which was redissolved in 5 mL of dichloromethane and 5 mL trifluoroacetic acid. After 5 hours the solvents were removed in vacuo and 5 mL of ethyl acetate and 5 mL of 10% sodium bicarbonate were added. The organic layer was separated, washed with brine, dried over magnesium sulfate and concentrated in vacuo to give 130 mg of the title compound as a white foam that was dissolved in ethyl acetate and treated with 1 equivalent of hydrochloric acid in 1.0M ether. The precipitate was collected, washed with ether and dried in vacuo to give 115 mg of the hydrochloride salt of (S)-3-(2-chloro-phenyl)-7-(2-hydroxy-1-methylethylamino)-1-(piperidin-4-yl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one.

Sources & evidence

ORD record
ord-b380a6c5f692485087a13135bb356fdd
Source dataset
uspto-grants-2002_09
Patent number
US06451804B1

Reaction notes

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