Trifluoroacetic acid → Diethyl (4-{[4-{[3-(methylsulfonyl)benzyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate

HRID 511207

反応式

HRID 511207 の反応式
Cl[C:2]1[N:7]=[C:6](Cl)[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.[CH3:13][S:14]([C:17]1[CH:18]=[C:19]([CH2:23][NH2:24])[CH:20]=[CH:21][CH:22]=1)(=[O:16])=[O:15].C(N(C(C)C)CC)(C)C.ClC1N=C(NCC2C=CC=C(S(C)(=O)=O)C=2)C(C(F)(F)F)=CN=1.ClC1C(C(F)(F)F)=CN=C(NCC2C=CC=C(S(C)(=O)=O)C=2)N=1.[NH2:80][C:81]1[CH:95]=[CH:94][C:84]([CH2:85][P:86](=[O:93])([O:90][CH2:91][CH3:92])[O:87][CH2:88][CH3:89])=[CH:83][CH:82]=1.C(O)(C(F)(F)F)=O>>[CH3:13][S:14]([C:17]1[CH:18]=[C:19]([CH:20]=[CH:21][CH:22]=1)[CH2:23][NH:24][C:6]1[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=[C:2]([NH:80][C:81]2[CH:82]=[CH:83][C:84]([CH2:85][P:86](=[O:93])([O:87][CH2:88][CH3:89])[O:90][CH2:91][CH3:92])=[CH:94][CH:95]=2)[N:7]=1)(=[O:15])=[O:16]

参加物

8

反応物 7

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 88358Diethyl p-aminobenzylphosphonateHCID 2760937(3-(Methylsulfonyl)phenyl)methanamineHCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidineHCID 866539992-Chloro-N-[3-(methylsulfonyl)benzyl]-5-(trifluoromethyl)pyrimidin-4-amine2 回HCID 866540004-chloro-N-[3-(methylsulfonyl)benzyl]-5-(trifluoromethyl)pyrimidin-2-amine

生成物 1

HCID 49821354Diethyl (4-{[4-{[3-(methylsulfonyl)benzyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate

実験手順

Reaction of 2,4-dichloro-5-(trifluoromethyl)pyrimidine XL with commercially available 1-[3-(methylsulfonyl)phenyl]methanamine and diisopropylethylamine at 0° C. overnight affords a mixture of 2-chloro-N-[3-(methylsulfonyl)benzyl]-5-(trifluoromethyl)pyrimidin-4-amine and 4-chloro-N-[3-(methylsulfonyl)benzyl]-5-(trifluoromethyl)pyrimidin-2-amine XLIVa/XLIVb. The crude mixture was crystallized from methylene chloride to afford a sample of the pure, undesired 2-substituted isomer XLIVb. The mother liquors were chromatographed over silica gel eluting with 1:1 hexane:ethyl acetate to yield a further pure sample of the 2-substituted isomer plus a sample of the desired 2-chloro-N-[3-(methylsulfonyl)benzyl]-5-(trifluoromethyl)pyrimidin-4-amine XLIVa. Reaction of this latter isomer with anilines such as diethyl (4-aminobenzyl)phosphonate in the presence of TFA and TFE under microwave irradiation yields the desired product (e.g. diethyl (4-{[4-{[3-(methylsulfonyl)benzyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate, Ex. 25).

後処理

  1. customaffords
  2. customThe crude mixture was crystallized from methylene chloride
  3. customto afford a sample of the pure, undesired 2-substituted isomer XLIVb
  4. customThe mother liquors were chromatographed over silica gel eluting with 1:1 hexane
  5. customethyl acetate to yield a further pure sample of the 2-substituted isomer
  6. customunder microwave irradiation

出典と根拠

ORDレコード
ord-b1432912a3714cfd801a1b065e85b4d2
出典データセット
uspto-grants-2015_08
特許番号
US09096624B2

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