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llms.txt · MCP 가이드개인정보처리방침 · 이용약관 · 지원v1.8.0
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Benzonitrile, 4-bromo- → (R)-4-(3-(3-(bis(4-methoxyphenyl)(phenyl)methylamino)-6,6-difluoro-5-methyl-2,5,6,7-tetrahydro-1,4-oxazepin-5-yl)-4-fluorophenylamino)benzonitrile

HRID 403230
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인쇄 미리보기

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HRID 403230 반응식
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:42])=[C:6]([C@:8]2([CH3:41])[C:14]([F:16])([F:15])[CH2:13][O:12][CH2:11][C:10]([NH:17][C:18]([C:33]3[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=3)([C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[N:9]2)[CH:7]=1.Br[C:44]1[CH:51]=[CH:50][C:47]([C:48]#[N:49])=[CH:46][CH:45]=1.CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd]>[CH3:32][O:31][C:28]1[CH:29]=[CH:30][C:25]([C:18]([C:33]2[CH:34]=[CH:35][C:36]([O:39][CH3:40])=[CH:37][CH:38]=2)([NH:17][C:10]2[CH2:11][O:12][CH2:13][C:14]([F:16])([F:15])[C@:8]([C:6]3[CH:7]=[C:2]([NH:1][C:44]4[CH:51]=[CH:50][C:47]([C:48]#[N:49])=[CH:46][CH:45]=4)[CH:3]=[CH:4][C:5]=3[F:42])([CH3:41])[N:9]=2)[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:26][CH:27]=1
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 4

HCID 12162Benzonitrile, 4-bromo-HCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 23676156Sodium t-butoxideHCID 68227104[(R)-5-(5-amino-2-fluoro-phenyl)-6,6-difluoro-5-methyl-2,5,6,7-tetrahydro-[1,4]oxazepin-3-yl]-[bis-(4-methoxy-phenyl)-phenyl-methyl]-amine

생성물 1

HCID 68227192
(R)-4-(3-(3-(bis(4-methoxyphenyl)(phenyl)methylamino)-6,6-difluoro-5-methyl-2,5,6,7-tetrahydro-1,4-oxazepin-5-yl)-4-fluorophenylamino)benzonitrile
수율 49%

시약·촉매·용매 2

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)촉매HCID 1140Toluene용매

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온도
107.5 °C

실험 절차

To a solution of [(R)-5-(5-amino-2-fluoro-phenyl)-6,6-difluoro-5-methyl-2,5,6,7-tetrahydro-[1,4]oxazepin-3-yl]-[bis-(4-methoxy-phenyl)-phenyl-methyl]-amine (intermediate A12A) (40 mg, 69.5 μmol) in toluene (0.6 ml) in a sealable tube was added subsequently at 23° C. and under an argon atmosphere 4-bromobenzonitrile (25.3 mg, 139 μmol), sodium tert-butoxide (13.4 mg, 139 μmol), 2-di-t-butylphosphino-2′,4′,6′-triisopropylbiphenyl (2.95 mg, 6.95 μmol) and tris(dibenzylideneacetone) dipalladium chloroform adduct (2.16 mg, 2.08 μmol), the tube was sealed and heated to 105 to 110° C. for 17 h. The mixture was cooled to 23° C., partitioned between saturated aqueous NaHCO3 and ethyl acetate, the organic layer was dried and evaporated to give the crude product, which was purified by silica gel flash chromatography with n-heptane/ethyl acetate and trituration with diethyl ether/pentane to give the (R)-4-(3-(3-(bis(4-methoxyphenyl)(phenyl)methylamino)-6,6-difluoro-5-methyl-2,5,6,7-tetrahydro-1,4-oxazepin-5-yl)-4-fluorophenylamino)benzonitrile (23 mg, 49%) as a light yellow crystalline. MS (ISN): m/z=675.5 [M−H]−.

후처리

  1. customthe tube was sealed
  2. temperatureThe mixture was cooled to 23° C.
  3. custompartitioned between saturated aqueous NaHCO3 and ethyl acetate
  4. customthe organic layer was dried
  5. customevaporated
  6. customto give the crude product, which
  7. customwas purified by silica gel flash chromatography with n-heptane/ethyl acetate and trituration with diethyl ether/pentane

출처 및 근거

ORD 기록
ord-87efb567ae2d45af8898bc7baeb2c744
출처 데이터셋
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08748418B2

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