Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → HCID 71251276, compound

HRID 1055126Notes

Reaction equation

[F:1][C:2]1[C:3]([NH:28][CH:29]([C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:30][C:31](O)=[O:32])=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[N:10](S(C3C=CC(C)=CC=3)(=O)=O)[CH:9]=2)=[N:6][CH:7]=1.C[N:39](C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1>[F:1][C:2]1[C:3]([NH:28][CH:29]([C:34]([CH3:35])([CH3:37])[CH3:36])[CH2:30][C:31]([NH2:39])=[O:32])=[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: 60 °C

Procedure

To a solution of racemic 3-(5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)-4,4-dimethylpentanoic acid, 163a, (0.50 g, 0.94 mmol) in 15 mL of THF was added HBTU (0.36 g, 0.95 mmol). The reaction was stirred for 15 minutes and then ammonia gas was bubbled through for 5 minutes. The reaction was allowed to stir for 12 hours and then concentrated to dryness. The residue was redissolved in 20 mL of MeOH and treated with 3 mL of 2N LiOH. The reaction was warmed to 60° C. for 3 hours and then concentrated to dryness. The residue was purified by silica gel chromatography (EtOAc) to afford 250 mg of desired product: LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=1.78 minutes (M+H) 375.45.

Workup

customammonia gas was bubbled through for 5 minutes
stirringto stir for 12 hours
concentrationconcentrated to dryness
dissolutionThe residue was redissolved in 20 mL of MeOH
additiontreated with 3 mL of 2N LiOH
concentrationconcentrated to dryness
customThe residue was purified by silica gel chromatography (EtOAc)

Sources & evidence

ORD record: ord-9c26cc190fc440c095b2057a0d568181
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394302B2

Reaction notes

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