Hydrogen Bromide → HCID 86268248, compound

HRID 710012Notes

Reaction equation

[F:1][C:2]1([F:35])[CH2:6][CH2:5][N:4]([C:7]2[N:12]=[C:11]([O:13]C)[C:10]([C:15]3[CH:20]=[CH:19][C:18]([O:21][C:22]4[CH:27]=[CH:26][N:25]=[C:24]([C:28]5[CH:29]=[N:30][N:31]([CH3:33])[CH:32]=5)[CH:23]=4)=[C:17]([CH3:34])[N:16]=3)=[CH:9][N:8]=2)[CH2:3]1.Br>CC(O)=O>[F:35][C:2]1([F:1])[CH2:6][CH2:5][N:4]([C:7]2[NH:12][C:11](=[O:13])[C:10]([C:15]3[CH:20]=[CH:19][C:18]([O:21][C:22]4[CH:27]=[CH:26][N:25]=[C:24]([C:28]5[CH:29]=[N:30][N:31]([CH3:33])[CH:32]=5)[CH:23]=4)=[C:17]([CH3:34])[N:16]=3)=[CH:9][N:8]=2)[CH2:3]1

Participants

Conditions

Temperature: 90 °C

Procedure

A solution of 2-(3,3-difluoropyrrolidin-1-yl)-4-methoxy-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidine (0.080 g, 0.167 mmol) in AcOH (3 mL) was treated with 48% hydrobromic acid (0.1 mL). The mixture was heated at 90° C. for 3 hours. The mixture was concentrated and the residue was treated with NaHCO3 and EtOAc. The mixture was stirred at RT. The solid was filtered and washed with water, EtOAc, and dried under vacuum to obtain 2-(3,3-difluoropyrrolidin-1-yl)-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-4(3H)-one (42 mg, 52.3% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.76 (br s, 1H), 8.36 (d, J=5.7 Hz, 1H), 8.28 (br s, 1H), 8.27 (s, 1H), 7.97 (s, 1H), 7.58 (br s, 1H), 7.24 (d, J=2.4 Hz, 1H), 6.64 (s, 1H), 3.96 (m, 2H), 3.85 (s, 3H), 3.76 (m, 2H), 2.54 (m, 2H), 2.37 (s, 3H), one proton is missing; MS (ESI) m/z: 466.2 (M+H+).

Workup

concentrationThe mixture was concentrated
additionthe residue was treated with NaHCO3 and EtOAc
filtrationThe solid was filtered
washwashed with water, EtOAc
customdried under vacuum

Sources & evidence

ORD record: ord-de820f3f8c4747ad976621fa8f7307c6
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181223B2

Reaction notes

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