(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidine → (S)-tert-butyl 1-(6-cyano-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-4-yl)pyrrolidin-3-ylcarbamate

HRID 60273Notes

Reaction equation

Cl[C:2]1[C:10]2[C:9]3[CH:11]=[C:12]([C:15]#[N:16])[N:13]=[CH:14][C:8]=3[N:7]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:6]=2[N:5]=[CH:4][CH:3]=1.[NH:25]1[CH2:29][CH2:28][C@H:27]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:26]1>CN(C)C(=O)C.C(OCC)(=O)C>[C:15]([C:12]1[N:13]=[CH:14][C:8]2[N:7]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:6]3[N:5]=[CH:4][CH:3]=[C:2]([N:25]4[CH2:29][CH2:28][C@H:27]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])[CH2:26]4)[C:10]=3[C:9]=2[CH:11]=1)#[N:16]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 4-chloro-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (590 mg, 1.6 mmol) and (S)-tert-butyl pyrrolidin-3-ylcarbamate (918 mg, 4.9 mmol) in N,N-dimethylacetamide (7.6 mL) was heated at 100° C. for 2 hours. The cooled reaction mixture was diluted with ethyl acetate (100 mL) and washed with water (40 mL). The organic layer was separated, dried over sodium sulfate, filtered, concentrated in vacuo, and purified by flash chromatography (silica, 12 g, ISCO, 0-90% ethyl acetate in heptane) to afford the title compound as a white solid, which was used in the next step without any further purification (530 mg, 63%).

Workup

customThe cooled reaction mixture
washwashed with water (40 mL)
customThe organic layer was separated
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
custompurified by flash chromatography (silica, 12 g, ISCO, 0-90% ethyl acetate in heptane)

Sources & evidence

ORD record: ord-60b02b90f16c401389712c0cb36c5edb
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440976B2

Reaction notes

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