Tetrahydrofuran → HCID 69185099, compound

HRID 2113590Notes

Reaction equation

HRID 2113590 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

3

Reactant 2

HCID 8028TetrahydrofuranHCID 185489534-(3-Chloro-4-fluorophenylamino)-6-fluoro-1,7-naphthyridine-3-carbonitrile

Product 1

HCID 69185099HCID 69185099, compoundYield 18.7%

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 (1S, 2R)-(+) norephdrine (0.96 g, 6.32 mmol) in 2 mL of THF. The reaction mixture was heated in a sealed vial in a microwave reactor at 140° C. for 50 min, then heated to 160° C. for 30 min. The crude product was purified by preparative HPLC and lyophilized to give a fluffy, yellow solid (26.4 mg, 18.7% yield): 1H NMR (400 MHz, DMSO-D6) δ ppm 1.03 (d, J=6.32 Hz, 3 H) 3.87-4.02 (m, 1 H) 4.67 (t, J=4.67 Hz, 1 H) 5.46 (d, J=4.29 Hz, 1 H) 6.43 (d, J=9.35 Hz, 1 H) 6.93 (s, 1 H) 7.12 (t, J=7.33 Hz, 1 H) 7.18-7.46 (m, 6 H) 7.48-7.55 (m, 1 H) 8.19 (s, 1 H) 8.75 (s, 1 H) 9.54 (s, 1 H); HRMS (ESI+) calcd for C24H19ClFN5O 448.13349, found (MH+), 448.1334.

Workup

  1. temperatureheated to 160° C. for 30 min
  2. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-df881d0830ca45efa7886f29bced62a5
Source dataset
uspto-grants-2008_10
Patent number
US07432279B2

Reaction notes

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