2,6-Difluorobenzoyl chloride → HCID 69070060, compound

HRID 1822019Notes

Reaction equation

[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[C:4]([Cl:6])=[O:5].[CH3:12][N:13]1[CH2:18][CH2:17][CH:16]([O:19][C:20]2[CH:21]=[C:22]([NH2:26])[CH:23]=[CH:24][CH:25]=2)[CH2:15][CH2:14]1>O1CCOCC1>[ClH:6].[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[C:4]([NH:26][C:22]1[CH:23]=[CH:24][CH:25]=[C:20]([O:19][CH:16]2[CH2:17][CH2:18][N:13]([CH3:12])[CH2:14][CH2:15]2)[CH:21]=1)=[O:5]

Participants

Conditions

Temperature: 110 °C

Procedure

Using a method similar to Example 1, add 2,6-difluoro-benzoyl chloride (0.68 ml, 0.544 mmol) to a solution of 3-(1-methyl-piperidin-4-yloxy)-phenylamine (preparation 24, 102 mg, 0.494 mmol) in dioxane (3.5 mL) in a sealed tube and heat at 110° C. for 2 hr. Purification by SCX column, eluting with ammonia (2.0 N in methanol) gives the title compound as the free base (154 mg, 90%). Following a method similar to Example 1 gives the title compound as the hydrochloride salt (147 mg, white solid). Mp: 136-8° C.; mass spectrum (free base, ion spray): m/z=347.1 (M+1); 1H NMR (free base, CDCl3): 7.62 (bs, N—H), 7.47 (s, 1H), 7.42 (t, J=2.0 Hz, 7.4 Hz, 1H), 7.24 (t, J=8.1 Hz, 1H), 7.04-6.97 (m, 3H), 6.73 (dd, J=2.0 Hz, 8.1 Hz, 1H), 4.43-4.35 (bm, 1H), 2.75-2.67 (bm, 2H), 2.39-2.33 (bm, 2H), 2.32 (s, 3H), 2.09-2.00 (bm, 2H), 1.92-1.82 (bm, 2H). Analysis calculated for C19H21ClF2N2O2.0.5H2O: C, 58.24; H, 5.66; N, 7.15. Found C, 58.56; H, 5.50; N, 7.12.

Workup

customPurification by SCX column
washeluting with ammonia (2.0 N in methanol)

Sources & evidence

ORD record: ord-90eb854f1df34d74a6268b3259508f3d
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07608629B2

Reaction notes

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