Triethylamine → N-[6-[[5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl]amino]norbornan-2-yl]pyrrolidine-1-carboxamide

HRID 527091Notes

Reaction equation

[F:1][C:2]1[C:3]([NH:18][CH:19]2[CH:24]3[CH2:25][CH:21]([CH2:22][CH:23]3C(O)=O)[CH2:20]2)=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[NH:10][CH:9]=2)=[N:6][CH:7]=1.C([N:31]([CH2:34]C)CC)C.N(P(OC1C=CC=CC=1)(OC1C=CC=CC=1)=[O:40])=[N+]=[N-].[NH:55]1[CH2:59][CH2:58][CH2:57][CH2:56]1>C1COCC1>[F:1][C:2]1[C:3]([NH:18][CH:19]2[CH:24]3[CH2:25][CH:21]([CH2:22][CH:23]3[NH:31][C:34]([N:55]3[CH2:59][CH2:58][CH2:57][CH2:56]3)=[O:40])[CH2:20]2)=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[NH:10][CH:9]=2)=[N:6][CH:7]=1

Participants

Conditions

Temperature: 95 °C

Procedure

To a solution of 6-[[5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl]amino]norbornane-2-carboxylic acid, 72j, (0.030 g, 0.078 mmol) in THF (0.375 mL) was added triethylamine (0.032 mL, 0.234 mmol) and (azido(phenoxy)phosphoryl)oxybenzene (0.018 mL, 0.085 mmol). The reaction mixture was heated to 95° C. for 2.5 hours, cooled down to 5° C., and treated with pyrrolidine (0.010 mL, 0.117 mmol). The reaction was stirred for 3 days at room temperature. The reaction mixture was injected directly into a preparatory HPLC system for purification to provide the product as a racemic mixture. The single enantiomers were obtained by separation using SFC chiral purification to afford 5.7 mg of the desired product as well as 1.4 mg of the enantiomer.

Workup

temperaturecooled down to 5° C.
customThe reaction mixture was injected directly into a preparatory HPLC system for purification
customto provide the product as a racemic mixture
customThe single enantiomers were obtained by separation
customSFC chiral purification

Sources & evidence

ORD record: ord-a340cc9616014a4caacf52f8e46d37fa
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09345708B2

Reaction notes

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