Diisopropylethylamine → N-((1-hydroxy-1H-spiro[benzo[c][1,2]oxaborole-3,1'-cyclopentan]-6-yl)methyl)-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)indolizine-8-carboxamide

HRID 1037116노트

반응식

HRID 1037116 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2([C:27]([F:30])([F:29])[F:28])[O:14][N:13]=[C:12]([C:15]3[N:16]4[C:20]([C:21]([C:24](O)=[O:25])=[CH:22][CH:23]=3)=[CH:19][CH:18]=[CH:17]4)[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.[NH2:65][CH2:66][C:67]1[CH:68]=[CH:69][C:70]2[C:74]3([CH2:78][CH2:77][CH2:76][CH2:75]3)[O:73][B:72]([OH:79])[C:71]=2[CH:80]=1>CN(C=O)C>[OH:79][B:72]1[C:71]2[CH:80]=[C:67]([CH2:66][NH:65][C:24]([C:21]3[C:20]4[N:16]([CH:17]=[CH:18][CH:19]=4)[C:15]([C:12]4[CH2:11][C:10]([C:4]5[CH:3]=[C:2]([Cl:1])[C:7]([Cl:8])=[C:6]([Cl:9])[CH:5]=5)([C:27]([F:28])([F:29])[F:30])[O:14][N:13]=4)=[CH:23][CH:22]=3)=[O:25])[CH:68]=[CH:69][C:70]=2[C:74]2([CH2:75][CH2:76][CH2:77][CH2:78]2)[O:73]1

참가 물질

6

반응물 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 866854806-(aminomethyl)-1H-spiro[benzo[c][1,2]oxa-borole-3,1'-cyclo-pentan]-1-ol hydrochlorideHCID 866855245-(5-(3,4,5-Trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)indolizine-8-carboxylic acid

생성물 1

HCID 71575831N-((1-hydroxy-1H-spiro[benzo[c][1,2]oxaborole-3,1'-cyclopentan]-6-yl)methyl)-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)indolizine-8-carboxamide

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A solution of 5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)indolizine-8-carboxylic acid (0.67 mmol) and DIPEA (346 mg, 2.68 mmol) in DMF (10 mL) can be stirred at rt for 5 min and then HATU (510 mg, 1.34 mmol) can be added. The mixture can be stirred for 10 min prior to the addition of 6-(aminomethyl)-1H-spiro[benzo[c][1,2]oxa-borole-3,1′-cyclo-pentan]-1-ol hydrochloride (202 mg, 0.80 mmol). And the resulting mixture can be stirred at rt overnight. It can be then concentrated under vacuum, and the residue can be partitioned between 1N HCl and ethyl acetate. The organic layer separated can be concentrated under vacuum, and the residue can be purified on column chromatography and prep-HPLC to provide the title product.

후처리

  1. stirringAnd the resulting mixture can be stirred at rt overnight
  2. concentrationIt can be then concentrated under vacuum
  3. customthe residue can be partitioned between 1N HCl and ethyl acetate
  4. customThe organic layer separated can
  5. concentrationbe concentrated under vacuum
  6. customthe residue can be purified on column chromatography

출처 및 근거

ORD 기록
ord-5a66bf75c7644ddf865edffae5a9208a
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08546357B2

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