1,2-Dichloroethane → 2,4-Difluoro-N-(3-(1-methylpiperidin-4-ylamino)-4-fluorophenyl)benzamide hydrochloride

HRID 1591892Notes

Reaction equation

[F:1][C:2]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[C:9]([NH2:14])[CH:8]=1)=[O:5].[CH3:20][N:21]1[CH2:26][CH2:25][C:24](=O)[CH2:23][CH2:22]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:46]CCCl>>[ClH:46].[F:1][C:2]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[C:9]([NH:14][CH:24]2[CH2:25][CH2:26][N:21]([CH3:20])[CH2:22][CH2:23]2)[CH:8]=1)=[O:5]

Participants

Reactant 5

HCID 111,2-Dichloroethane

HCID 176Acetic Acid

HCID 740491-Methyl-4-piperidone

HCID 5049666Sodium triacetoxyborohydride

HCID 167726472,4-Difluoro-N-(3-amino-4-fluorophenyl)benzamide

Product 1

HCID 669390042,4-Difluoro-N-(3-(1-methylpiperidin-4-ylamino)-4-fluorophenyl)benzamide hydrochlorideYield 70%

Procedure

Using a procedure similar Example 24 using 2,4-difluoro-N-(3-amino-4-fluorophenyl)benzamide (Preparation 16,452 mg, 1.7 mmol), 1-methyl-4-piperidone (384 mg, 0.42 mL, 3.4 mmol), 1,2-dichloroethane (15 mL), powdered molecular sieves 4 Å (1 g), glacial acetic acid (306 mg, 0.3 mL, 5.1 mmol), sodium triacetoxyborohydride (900 mg, 4.25 mmol) to obtain the free base of the title compound (434 mg, 70% yield) and the title compound: mass spectrum (ion spray): m/z=364.1 (M+1); analysis calc'd for C19H20F3N3O.HCl.H2O: C, 54.61; H, 5.55; N, 10.06. Found: C, 54.48; H, 5.36; N, 9.93. 1H NMR δ (methanol-d4) 7.79(m, 1H), 7.63(d, 1H), 7.11(m, 4H), 3.74(m, 1H), 3.62(d, 2H), 3.30(dd, 2H), 2.88(s, 3H), 2.36(d, 2H), 1.93(m, 2H)

Sources & evidence

ORD record: ord-c26cedb3b8884e348bd0b30b4612e6a5
Source dataset: uspto-grants-2007_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07291632B2

Reaction notes

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