Acetic Acid → Tert-butyl 4-(3-(3,5-dichlorophenylamino)-1H-1,2,4-triazol-5-ylamino)piperidine-1-carboxylate

HRID 1486592노트

반응식

HRID 1486592 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[N:14]=[C:13]([NH2:15])[NH:12][N:11]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.ClC1C=C(N=C=S)C=C(Cl)C=1C#N.O=[C:30]1[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]1.C(O)(=O)C>CO>[C:39]([O:38][C:36]([N:33]1[CH2:34][CH2:35][CH:30]([NH:15][C:13]2[NH:12][N:11]=[C:10]([NH:9][C:4]3[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([Cl:1])[CH:3]=3)[N:14]=2)[CH2:31][CH2:32]1)=[O:37])([CH3:42])([CH3:40])[CH3:41]

참가 물질

6

반응물 4

HCID 176Acetic AcidHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 727146143-Amino-5-(3,5-dichloroanilino)-s-triazoleHCID 867076002,6-Dichloro-4-isothiocyanatobenzonitrile

생성물 1

HCID 178452086Tert-butyl 4-(3-(3,5-dichlorophenylamino)-1H-1,2,4-triazol-5-ylamino)piperidine-1-carboxylate수율 88%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

To a stirred solution of N3-(3,5-dichlorophenyl)-1H-1,2,4-triazole-3,5-diamine Intermediate 2 (122 mg, 0.5 mmol) in 10 ml of methanol, tert-butyl 4-oxopiperidine-1-carboxylate (102 mg, 0.512 mmol), was added acetic acid (0.05 mL). The mixture was stirred at rt for 15 min, after which picolineborane (112 mg, 1.047 mmol) was added. The mixture was stirred at rt overnight. LCMS indicated 87% product and 13% SM. Additional picolineborane (50 mg, 0.467 mmol) was added and the mixture was stirred for an additional 24 hours. The solvent was removed under reduced pressure and the residue was dissolved in methylene chloride and treated with saturated sodium bicarbonate to pH=9. The organic layer was separated and the aqueous layer was extracted with methylene chloride (3×10 mL). The solvent was reduced to about 4 mL and the residue was loaded onto a silica gel column. Eluting with 5% methanol/methylene chloride gave 188 mg (88%) of desired product as white solid. MS +m/z: 427.0 (M+H)+

후처리

  1. additionafter which picolineborane (112 mg, 1.047 mmol) was added
  2. stirringThe mixture was stirred at rt overnight
  3. additionAdditional picolineborane (50 mg, 0.467 mmol) was added
  4. stirringthe mixture was stirred for an additional 24 hours
  5. customThe solvent was removed under reduced pressure
  6. dissolutionthe residue was dissolved in methylene chloride
  7. additiontreated with saturated sodium bicarbonate to pH=9
  8. customThe organic layer was separated
  9. extractionthe aqueous layer was extracted with methylene chloride (3×10 mL)
  10. washEluting with 5% methanol/methylene chloride

출처 및 근거

ORD 기록
ord-a26851db74834ced86f2e4f6eac1ead8
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09428469B2

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