Triethylamine → 8-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)methyl)indolizine-5-carboxamide

HRID 1037084ノート

反応式

HRID 1037084 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:26]([F:29])([F:28])[F:27])[O:13][N:12]=[C:11]([C:14]3[C:22]4[N:18]([CH:19]=[CH:20][CH:21]=4)[C:17]([C:23]([OH:25])=O)=[CH:16][CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.Cl.[NH2:62][CH2:63][C:64]1[CH:65]=[CH:66][C:67]2[C:71]([CH3:73])([CH3:72])[O:70][B:69]([OH:74])[C:68]=2[CH:75]=1>CN(C=O)C.CC(=O)OCC>[Cl:8][C:6]1[CH:5]=[C:4]([C:9]2([C:26]([F:28])([F:27])[F:29])[O:13][N:12]=[C:11]([C:14]3[C:22]4[N:18]([CH:19]=[CH:20][CH:21]=4)[C:17]([C:23]([NH:62][CH2:63][C:64]4[CH:65]=[CH:66][C:67]5[C:71]([CH3:73])([CH3:72])[O:70][B:69]([OH:74])[C:68]=5[CH:75]=4)=[O:25])=[CH:16][CH:15]=3)[CH2:10]2)[CH:3]=[C:2]([Cl:1])[CH:7]=1

参加物

7

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 86685457HCID 86685457、化合物HCID 866855228-[5-(Trifluoromethyl)-5-(3,5-dichlorophenyl)-2-isoxazoline-3-yl]indolizine-5-carboxylic acid

生成物 1

HCID 715763408-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)methyl)indolizine-5-carboxamide収率 40.6%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of 8-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)indolizine-5-carboxylic acid (23 mg, 0.052 mmol), HATU (30 mg, 0.078 mmol) and Et3N (0.02 mL, 0.104 mmol) in DMF (10 mL) was added 6-(aminomethyl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol hydrochloride (24 mg, 0.104 mmol). The mixture was stirred at rt overnight. EA (50 mL) was added and the mixture was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by prep-HPLC to give the title compound 8-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)methyl)indolizine-5-carboxamide (13 mg, yield 40%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 9.50 (t, J=6.0 Hz, 1H), 9.05 (s, 1H), 8.19 (s, 1H), 7.83 (s, 1H), 7.67 (s, 3H), 7.47 (d, J=8.0 Hz, 1H), 7.40 (d, J=8.0 Hz, 1H), 7.21 (d, J=8.0 Hz, 1H), 7.17 (d, J=8.0 Hz, 1H), 7.11 (s, 1H), 6.94 (s, 1H), 4.57 (d, J=6.0 Hz, 2H), 4.48 (d, J=18.0 Hz, 1H), 4.38 (d, J=18.0 Hz, 1H), 1.44 (s, 6H) ppm; HPLC purity: 100.0% at 220 nm and 100.0% at 254 nm; MS: m/z=616.0 (M+1, ESI+).

後処理

  1. washthe mixture was washed with brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by prep-HPLC

出典と根拠

ORDレコード
ord-6e309d358b804b89989f6d9ed87b327e
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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