Triethylamine → 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazol-3-yl)-N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)-methyl)-2-methylbenzamide

HRID 1037010ノート

反応式

HRID 1037010 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:24]([F:27])([F:26])[F:25])[O:13][N:12]=[C:11]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[C:16]([CH3:23])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.CCN(CC)CC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:60][CH2:61][C:62]1[CH:63]=[CH:64][C:65]2[C:69]([CH3:71])([CH3:70])[O:68][B:67]([OH:72])[C:66]=2[CH:73]=1>CC#N>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:24]([F:25])([F:26])[F:27])[O:13][N:12]=[C:11]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([NH:60][CH2:61][C:62]4[CH:63]=[CH:64][C:65]5[C:69]([CH3:71])([CH3:70])[O:68][B:67]([OH:72])[C:66]=5[CH:73]=4)=[O:20])=[C:16]([CH3:23])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

参加物

6

反応物 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 231598114-(5-(3,5-Dichlorophenyl)-5-(tri fluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acidHCID 86685457HCID 86685457、化合物

生成物 1

HCID 715759424-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazol-3-yl)-N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)-methyl)-2-methylbenzamide収率 21.4%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

A solution of 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (1.65 g, 3.95 mmol) and Et3N (1.6 g, 15.8 mmol) in MeCN (35 ml) was stirred at rt for 5 min and then HATU (3 g, 7.9 mmol) was added. The mixture was stirred for 10 min prior to the addition of 6-(aminomethyl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol hydrochloride (906 mg, 4.74 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 column chromatography and preparative HPLC to provide the product (500 mg, yield 21%). 1H NMR (300 MHz, DMSO-d6): δ 9.05 (s, 1H), 8.92 (s, 1H), 7.82 (s, 1H), 7.61 (m, 5H), 7.40 (m, 3H), 4.49 (d, 2H), 4.37 (d, 2H), 2.39 (s, 3H), 1.44 (s, 6H) ppm; HPLC purity: 97.4% at 220 nm and 98.1% at 254 nm; MS: m/z=591.3 (M+H, ESI+).

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 column chromatography and preparative HPLC

出典と根拠

ORDレコード
ord-1dde1a5fae3f40a380d3e0f6a297166a
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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