Tetrahydrofuran → HCID 86609509, compound

HRID 2113591Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][N:16]=[C:17](F)[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:21]#[N:22])[CH:5]=[CH:6][C:7]=1[F:8].[CH2:23]1[CH2:27][O:26][CH2:25][CH2:24]1>>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][N:16]=[C:17]([NH:9][C@@H:4]([CH3:3])[C@H:25]([OH:26])[C:24]4[CH:23]=[CH:27][CH:7]=[CH:6][CH:5]=4)[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:21]#[N:22])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

Reactant 2

HCID 8028Tetrahydrofuran

HCID 185489534-(3-Chloro-4-fluorophenylamino)-6-fluoro-1,7-naphthyridine-3-carbonitrile

Product 1

HCID 86609509HCID 86609509, compoundYield 18.9%

Conditions

Temperature: 140 °C

Procedure

Following the procedure described above in Example 51, 4-(3-Chloro-4-fluoro-phenylamino)-6-fluoro-[1,7]naphthyridine-3-carbonitrile (0.10 g, 0.32 mmol) was reacted with (1R, 2S)-(−) norephdrine (0.96 g, 6.32 mmol) in 2 mL of THF. The reaction mixture was heated up in a sealed vial in a microwave reactor at 140° C. for 105 min. The crude product was purified by preparative HPLC and lyophilized to give a fluffy, yellow solid (26.7 mg, 18.9% yield): 1H NMR (400 MHz, DMSO-D6) δ ppm 1.09 (d, J=6.32 Hz, 3 H) 3.94-4.06 (m, 1 H) 4.73 (t, J=4.80 Hz, 1 H) 5.52 (d, J=4.29 Hz, 1 H) 6.49 (d, J=9.35 Hz, 1 H) 6.98 (s, 1 H) 7.18 (t, J=7.20 Hz, 1 H) 7.22-7.51 (m, 6 H) 7.58 (d, J=4.29 Hz, 1 H) 8.25 (s, 1 H) 8.81 (s, 1 H) 9.60 (s, 1 H); HRMS (ESI+) calcd for C24H19ClFN5O 448.13349, found (MH+) 448.1334.

Workup

customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record: ord-c78144b995764b01a8683ed62fb099f9
Source dataset: uspto-grants-2008_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07432279B2

Reaction notes

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