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O-Xylene → (1,1-dimethylethyl) 3-[[5-methyl-6-[4-(1,2,3,4-tetrahydro-1,8-naphthyridin-7-yl)-1-piperidinyl]-4-pyrimidinyl]amino]-N-[(phenylmethoxy)carbonyl]alaninate

HRID 2358202
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인쇄 미리보기

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HRID 2358202 반응식
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][CH2:9][C@@H:10]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[NH:11][C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[C:3]=1[CH3:29].[NH:30]1[CH2:35][CH2:34][CH:33]([C:36]2[N:45]=[C:44]3[C:39]([CH2:40][CH2:41][CH2:42][NH:43]3)=[CH:38][CH:37]=2)[CH2:32][CH2:31]1.C1(C)C(C)=CC=CC=1.C(=O)(O)[O-].[Na+]>C(N(C(C)C)CC)(C)C.O.C(OCC)(=O)C.CO.C(N(CC)CC)C.ClCCl.C(OCC)(=O)C>[NH:43]1[C:44]2[C:39](=[CH:38][CH:37]=[C:36]([CH:33]3[CH2:34][CH2:35][N:30]([C:2]4[N:7]=[CH:6][N:5]=[C:4]([NH:8][CH2:9][C@@H:10]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[NH:11][C:12]([O:14][CH2:15][C:16]5[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=5)=[O:13])[C:3]=4[CH3:29])[CH2:31][CH2:32]3)[N:45]=2)[CH2:40][CH2:41][CH2:42]1
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참가 물질

9

반응물 4

HCID 7237O-XyleneHCID 516892Sodium BicarbonateHCID 113903267-(4-Piperidinyl)-1,2,3,4-tetrahydro[1,8]naphthyridineHCID 12094347(1,1-Dimethylethyl)-3-[(6-chloro-5-methyl-4-pyrimidinyl)amino]-n-[(phenylmethoxy)carbonyl]alaninate

생성물 1

HCID 12094349(1,1-dimethylethyl) 3-[[5-methyl-6-[4-(1,2,3,4-tetrahydro-1,8-naphthyridin-7-yl)-1-piperidinyl]-4-pyrimidinyl]amino]-N-[(phenylmethoxy)carbonyl]alaninate
수율 6%

시약·촉매·용매 4

HCID 962Water용매HCID 8857Ethyl Acetate용매2회HCID 81531Diisopropylethylamine용매HCID 22169411Ethyl acetate methanol triethylamine dichloromethane용매

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온도
120 °C

실험 절차

A mixture of 370 mg (0.88 mmoles) of (1,1-dimethylethyl) 3-[(6-chloro-5-methyl-4-pyrimidinyl)amino]-N-[(phenylmethoxy)carbonyl]alaninate and 1.0 g (1.79 mmoles) of 1,2,3,4-tetrahydro-7-(4-piperidinyl)-1,8-naphthyridine, tris (trifluoroacetate) (prepared according to Patents EP 1065207 or WO 0078317) in 1 ml of diisopropylethylamine is heated at 120° C. for 2 hours. Then 10 ml of xylene is added and the medium is taken to reflux for 4 hours. The reaction medium is taken up in a mixture of water, ethyl acetate and a saturated solution of sodium bicarbonate. The organic phase is decanted and the aqueous phase is reextracted with ethyl acetate. The combined organic phases are dried over magnesium sulphate and evaporated to dryness under vacuum and the residue is chromatographed on silicagel with a gradient of 100% ethyl acetate to a mixture of ethyl acetate-methanol-triethylamine-dichloromethane 50-10-10-50.32 mg (Yield=6%) of expected product is obtained and 200 mg (54%) of chlorinated starting product is recovered.

후처리

  1. temperatureto reflux for 4 hours
  2. customThe organic phase is decanted
  3. dry with materialThe combined organic phases are dried over magnesium sulphate
  4. customevaporated to dryness under vacuum

출처 및 근거

ORD 기록
ord-6b003734f3d34dfa960e0e65c9e99c6f
출처 데이터셋
uspto-grants-2010_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07763621B2

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