2,6-Xylenol, 4-nitro- → 2-chloro-N4-(3,5-dimethyl-4-hydroxyphenyl)-5-fluoro-4-pyrimidineamine

HRID 603709Notes

Reaction equation

HRID 603709 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([CH3:11])[C:3]=1[OH:12].NC1C=C(C)C(O)=C(C)C=1.C1COC2C=CC(NC3C(F)=CN=C(NC4C=CC=C(O)C=4)N=3)=CC=2O1.[Cl:49][C:50]1[N:55]=[C:54](Cl)[C:53]([F:57])=[CH:52][N:51]=1>>[Cl:49][C:50]1[N:55]=[C:54]([NH:8][C:6]2[CH:7]=[C:2]([CH3:1])[C:3]([OH:12])=[C:4]([CH3:11])[CH:5]=2)[C:53]([F:57])=[CH:52][N:51]=1

Participants

5

Reactant 4

HCID 170302,6-Xylenol, 4-nitro-HCID 826684-Amino-2,6-dimethylphenol2×HCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 22060334N4-(3,4-ethylenedioxyphenyl)-5-fluoro-N2-(3-hydroxyphenyl)-2,4-primidinediamine

Product 1

HCID 220604042-chloro-N4-(3,5-dimethyl-4-hydroxyphenyl)-5-fluoro-4-pyrimidineamine

Procedure

Using general hydrogenation conditions, 2,6-dimethyl-4-nitrophenol was reduced to 4-amino-2,6-dimethylphenol. In a manner analogous to the preparation of N4-(3,4-ethylenedioxyphenyl)-5-fluoro-N2-(3-hydroxyphenyl)-2,4-pyrimidinediamine, the reaction of 4-amino-2,6-dimethylphenol (823 mg, 6 mmol) and 2,4-dichloro-5-fluoropyrimidine (500 mg, 3 mmol) gave 2-chloro-N4-(3,5-dimethyl-4-hydroxyphenyl)-5-fluoro-4-pyrimidineamine. Compound 2-chloro-N4-(3,5-dimethyl-4-hydroxyphenyl)-5-fluoro-4-pyrimidineamine (500 mg, 1.87 mmol) and 3-(methoxycarbonylmethyleneoxy)aniline (500 mg, 2.76 mmol) reacted to give N4-(3,5-dimethyl-4-hydroxyphenyl)-5-fluoro-N2-(3-methoxycarbonylmethyleneoxyphenyl)-2,4-pyrimidinediamine (500 mg, 65%). 1H NMR (CD3OD): δ 2.16 (s, 6H), 3.76 (s, 3H), 4.51 (s, 2H), 6.79 (ddd, J=0.9, 2.4 and 8.1 Hz, 1H), 7.01-7.06 (m, 2H), 7.15 (s, 2H), 7.26 (t, J=8.1 Hz, 1H), 7.93 (d, J=5.7 Hz, 1H); 19F NMR (282 MHz, CD3OD): 6-163.31; LCMS: ret. time: 20.44 min.; purity: 84.25%; MS (m/e): 413.03 (MH+).

Sources & evidence

ORD record
ord-09d378c3b08247eeb2c2445e3e4807f0
Source dataset
uspto-grants-2011_03
Patent number
US07906644B2

Reaction notes

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