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Methanol → 2-((cyclopropylamino)(5-fluoropyridin-2-yl)methyl)-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine

HRID 473175
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인쇄 미리보기

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HRID 473175 반응식
[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([C:10]2[N:19]=[C:18]([NH:20][C:21]3[CH:25]=[C:24]([CH3:26])[NH:23][N:22]=3)[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]=2)=O)=[N:6][CH:7]=1.[CH:27]1([NH2:30])[CH2:29][CH2:28]1.[BH4-].[Na+].CO>CC(O)C.CC(O)=O>[CH:27]1([NH:30][CH:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][N:6]=2)[C:10]2[N:19]=[C:18]([NH:20][C:21]3[CH:25]=[C:24]([CH3:26])[NH:23][N:22]=3)[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]=2)[CH2:29][CH2:28]1
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 4

HCID 887MethanolHCID 69828Cyclopropylamine2회HCID 4311764Sodium borohydride2회HCID 56848496(5-fluoropyridin-2-yl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanone

생성물 1

HCID 666135922-((cyclopropylamino)(5-fluoropyridin-2-yl)methyl)-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine

시약·촉매·용매 2

HCID 176
Acetic Acid
용매
HCID 3776Isopropanol용매2회

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온도
140 °C

실험 절차

To (5-fluoropyridin-2-yl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanone from Example 1 (1 equiv) in 2-propanol are added cyclopropylamine (5 equiv) and 3 Å(8-12 mesh) molecular sieves, and the mixture is heated at 140° C. in a microwave reactor. Additional cyclopropylamine is added and microwave or conventional heating is continued until the reaction is substantially complete according to NMR. Then a suspension of sodium borohydride (10 equiv) in 2-propanol is added and the mixture is stirred at rt. Methanol, additional sodium borohydride, and traces of HOAc are added as necessary until the reaction is substantially complete, then the mixture is filtered and the filtrate is concentrated. DMSO is added and the mixture is purified by preparative HPLC to afford 2-((cyclopropylamino)(5-fluoropyridin-2-yl)methyl)-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine.

후처리

  1. temperaturemicrowave or conventional heating
  2. additionis added
  3. filtrationthe mixture is filtered
  4. concentrationthe filtrate is concentrated
  5. additionDMSO is added
  6. customthe mixture is purified by preparative HPLC

출처 및 근거

ORD 기록
ord-8460774673b3436aaa6b129d8ee7c567
출처 데이터셋
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08633207B2

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