Diisopropylethylamine → N-((3,3-Bis(fluoromethyl)-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)methyl)-2-methyl-4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzamide

HRID 1037030ノート

反応式

HRID 1037030 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2([C:25]([F:28])([F:27])[F:26])[O:14][N:13]=[C:12]([C:15]3[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[C:17]([CH3:24])[CH:16]=3)[CH2:11]2)[CH:5]=[C:6]([Cl:9])[C:7]=1[Cl:8].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:63][CH2:64][C:65]1[CH:66]=[CH:67][C:68]2[C:72]([CH2:75][F:76])([CH2:73][F:74])[O:71][B:70]([OH:77])[C:69]=2[CH:78]=1>CN(C=O)C>[F:76][CH2:75][C:72]1([CH2:73][F:74])[O:71][B:70]([OH:77])[C:69]2[CH:78]=[C:65]([CH2:64][NH:63][C:19](=[O:21])[C:18]3[CH:22]=[CH:23][C:15]([C:12]4[CH2:11][C:10]([C:4]5[CH:5]=[C:6]([Cl:9])[C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=5)([C:25]([F:27])([F:26])[F:28])[O:14][N:13]=4)=[CH:16][C:17]=3[CH3:24])[CH:66]=[CH:67][C:68]1=2

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 866854502-Methyl-4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzoic acidHCID 866854756-(aminomethyl)-3,3-bis(fluoromethyl)benzo[c][1,2]oxaborol-1(3H)-ol hydrochloride

生成物 1

HCID 71576147N-((3,3-Bis(fluoromethyl)-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)methyl)-2-methyl-4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzamide収率 33%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A solution of 4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (100 mg, 0.22 mmol) and DIPEA (114 mg, 0.88 mmol) in DMF (5 mL) was stirred at rt for 5 min and then HATU (169 mg, 0.44 mmol) was added. The mixture was stirred for 10 min prior to the addition of 6-(aminomethyl)-3,3-bis(fluoromethyl)benzo[c][1,2]oxaborol-1(3H)-ol hydrochloride (116 mg, 0.44 mmol). And the resulting mixture was stirred at rt overnight. It was then concentrated under vacuum, and the residue was partitioned between 1N HCl and ethyl acetate. The organic layer separated was concentrated under vacuum, and the residue was purified by prep-TLC to provide the product (48 mg, 33%). 1H NMR (400 MHz, DMSO-d6): δ 8.89 (s, 1H), 7.82 (s, 2H), 7.59-7.57 (m, 2H), 7.49-7.44 (m, 3H), 7.33-7.31 (m, 2H), 4.61-4.31 (m, 8H), 2.36 (s, 3H) ppm; HPLC purity: 97.63% at 220 nm and 97.48% at 254 nm.

後処理

  1. stirringAnd the resulting mixture was stirred at rt overnight
  2. concentrationIt was then concentrated under vacuum
  3. customthe residue was partitioned between 1N HCl and ethyl acetate
  4. customThe organic layer separated
  5. concentrationwas concentrated under vacuum
  6. customthe residue was purified by prep-TLC

出典と根拠

ORDレコード
ord-40e248f817e64ae4a902b577276ca30d
出典データセット
uspto-grants-2013_10
特許番号
US08546357B2

反応ノート

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