Potassium Carbonate → 1-Pyrrolidinecarboxylic acid, 3-[[5,6,7,8-tetrahydro-6-(phenylmethyl)pyrido[4,3-d]pyrimidin-4-yl]amino]-, 1,1-dimethylethyl ester, (3S)-

HRID 242316

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([NH2:13])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:14]([N:21]1[CH2:31][CH2:30][C:24]2[N:25]=[CH:26][N:27]=[C:28](Cl)[C:23]=2[CH2:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C([O-])([O-])=O.[K+].[K+]>CN1C(=O)CCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([NH:13][C:28]2[C:23]3[CH2:22][N:21]([CH2:14][C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)[CH2:31][CH2:30][C:24]=3[N:25]=[CH:26][N:27]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 120 °C

Procedure

(S)-tert-Butyl-3-aminopyrrolidine-1-carboxylate (50 g, 192.5 mmol) was added to 6-benzyl-4-chloro-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine (39.440 g, 211.8 mmol) in NMP (200 mL) solution followed by the addition of K2CO3 (39.9 g, 288.8 mmol). The mixture was heated to 120° C. for 20 h. The mixture was allowed to cool, partitioned between water (300 mL) and ethylacetate (500 mL). the bottom aqueous phase was discarded and the upper organic phase was washed with brine (150 mL) and concentrated in vacuo to provide crude (S)-3-(6-benzyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-ylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester as a pale yellow foam (76.44 g, 97% yield).

Workup

temperatureto cool
custompartitioned between water (300 mL) and ethylacetate (500 mL)
washthe upper organic phase was washed with brine (150 mL)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-c02289d97acb40bd9157b437a574d352
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653092B2

Linked notes

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