Sodium hydride → USRE48711, Example 95

HRID 389633Notes

Reaction equation

HRID 389633 reaction equation
[H-].[Na+].[CH:3]1([N:6]2[CH:10]=[N:9][N:8]=[C:7]2[C:11]2[CH:12]=[C:13]([NH:17][C:18]([C:20]3[CH:25]=[C:24]([C:26]4[CH:27]=[N:28][C:29](F)=[CH:30][CH:31]=4)[CH:23]=[CH:22][N:21]=3)=[O:19])[CH:14]=[CH:15][CH:16]=2)[CH2:5][CH2:4]1.[CH:33]1([OH:37])[CH2:36][CH2:35][CH2:34]1>>[CH:33]1([O:37][C:29]2[N:28]=[CH:27][C:26]([C:24]3[CH:23]=[CH:22][N:21]=[C:20]([C:18]([NH:17][C:13]4[CH:14]=[CH:15][CH:16]=[C:11]([C:7]5[N:6]([CH:3]6[CH2:5][CH2:4]6)[CH:10]=[N:9][N:8]=5)[CH:12]=4)=[O:19])[CH:25]=3)=[CH:31][CH:30]=2)[CH2:36][CH2:35][CH2:34]1

Participants

4

Reactant 3

HCID 24758Sodium hydrideHCID 76218Cyclobutanol2×HCID 58102944USRE48711, Example 93

Product 1

HCID 49868839USRE48711, Example 95Yield 55%

Procedure

Sodium hydride (60% in mineral oil, 15 mg, 0.38 mmol) was added to 0.5 mL of cyclobutanol and the reaction mixture was stirred for 10 minutes at room temperature. (N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-fluoro-3,4′-bipyridine-2′-carboxamide) (24 mg, 0.06 mmol) in cyclobutanol (0.2 mL) was added and the reaction mixture was heated to 90° C. for 30 minutes. The reaction mixture was concentrated under reduced pressure, neutralized with 1 M HCl and purified by reverse-phase HPLC to give the product as a white powder (15 mg, 55% yield). C26H24N6O2. 453.1 (M+1). 1H NMR (DMSO) d 10.92 (s, 1H), 8.79 (d, J=5.2 Hz, 1H), 8.72 (d, J=2.4 Hz, 1H), 8.62 (s, 1H), 8.58 (s, 1H), 8.41 (d, J=1.2 Hz, 1H), 8.26 (dd, J=4.8, 2.4 Hz, 1H), 8.07 (d, J=−8.0 Hz, 1H), 8.03 (dd, J=5.2, 2.0 Hz, 1H), 7.68 (d, J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 6.95 (d, J=8.8 Hz, 1H), 5.22 (p, J=7.6 Hz, 1H), 3.66 (m, 1H), 2.45 (m, 2H), 2.10 (m, 2H), 1.85 (m, 1H), 1.70 (m, 1H), 1.08 (m, 2H), 0.95 (m, 2H).

Workup

  1. temperaturethe reaction mixture was heated to 90° C. for 30 minutes
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. custompurified by reverse-phase HPLC

Sources & evidence

ORD record
ord-c62e806cf8c24d8588af65c75f8b6508
Source dataset
uspto-grants-2013_02
Patent number
US08378108B2

Reaction notes

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