Triethylamine → {(R)-1-[(S)-1-(3-Amino-1-cyclopropyl-6-fluoro-8-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-7-yl)-pyrrolidin-3-yl]-ethyl}-carbamic acid tert-butyl ester

HRID 729417

반응식

HRID 729417 반응식
[NH2:1][N:2]1[C:11](=[O:12])[C:10]2[C:5](=[C:6]([CH3:15])[C:7](F)=[C:8]([F:13])[CH:9]=2)[N:4]([CH:16]2[CH2:18][CH2:17]2)[C:3]1=[O:19].[C:20]([O:24][C:25](=[O:34])[NH:26][C@H:27]([C@@H:29]1[CH2:33][CH2:32][NH:31][CH2:30]1)[CH3:28])([CH3:23])([CH3:22])[CH3:21].C(N(CC)CC)C.N1CCCC1>O.CS(C)=O>[C:20]([O:24][C:25](=[O:34])[NH:26][C@@H:27]([C@H:29]1[CH2:33][CH2:32][N:31]([C:7]2[C:6]([CH3:15])=[C:5]3[C:10]([C:11](=[O:12])[N:2]([NH2:1])[C:3](=[O:19])[N:4]3[CH:16]3[CH2:18][CH2:17]3)=[CH:9][C:8]=2[F:13])[CH2:30]1)[CH3:28])([CH3:21])([CH3:22])[CH3:23]

참가 물질

7

반응물 4

HCID 8471Triethylamine2회HCID 31268PyrrolidineHCID 10242357(3R,1S)-3-(1-(t-butoxycarbonylamino)ethyl)pyrrolidineHCID 111614632,4(1H,3H)-Quinazolinedione, 3-amino-1-cyclopropyl-6,7-difluoro-8-methyl-

생성물 1

HCID 58681880{(R)-1-[(S)-1-(3-Amino-1-cyclopropyl-6-fluoro-8-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-7-yl)-pyrrolidin-3-yl]-ethyl}-carbamic acid tert-butyl ester수율 45.6%

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 962Water용매

반응 조건

온도
120 °C

실험 절차

A solution of 0.5 g (1.9 mmol) of 3-amino-1-cyclopropyl-6,7-difluoro-8-methyl-1H-quinazoline-2,4-dione (Example 24e), 0.64 g (3.0 mmol) of ((S)-(R)-1-pyrrolidin-3-ylethyl)carbamic acid tert-butyl ester, 0.81 g (8.0 mmol) of triethylamine and 10 mL of dimethyl sulfoxide is heated at 110° C. for 24 hours. After thin layer chromatography showed incomplete reaction, an additional 0.43 g (2.0 mmol) of pyrrolidine derivative and 0.81 g (8.0 mmol) of triethylamine are added and the reaction is heated at 120° C. for 18 hours. The reaction mixture is cooled to room temperature, poured into 200 mL of ice and water and extracted with ethyl acetate (2×125 mL). The combined organic layers are washed with water, dried (MgSO4), filtered and evaporated in vacuo to give 1.1 g of crude product. Chromatography on flash grade silica gel (230-400 mesh) eluting with ethyl acetate provided 0.4 g of the title compound, mp 86-88° C.

후처리

  1. customreaction
  2. temperatureThe reaction mixture is cooled to room temperature
  3. extractionextracted with ethyl acetate (2×125 mL)
  4. washThe combined organic layers are washed with water
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customto give 1.1 g of crude product
  9. washChromatography on flash grade silica gel (230-400 mesh) eluting with ethyl acetate

출처 및 근거

ORD 기록
ord-c76354094ae04b0b8ee09bb6d9077d59
출처 데이터셋
uspto-grants-2009_09
특허 번호
US07582627B2

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