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5-Bromopyrimidine → HCID 69550769, 화합물

HRID 348554
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HRID 348554 반응식
Br[C:2]1[CH:3]=[N:4][CH:5]=[N:6][CH:7]=1.[C:8]1([C@H:14]2[CH2:19][CH2:18][CH2:17][CH2:16][C@H:15]2[N:20]2[CH2:25][CH2:24][CH:23]([NH2:26])[CH2:22][CH2:21]2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.C(OCC)C>[C:8]1([C@H:14]2[CH2:19][CH2:18][CH2:17][CH2:16][C@H:15]2[N:20]2[CH2:25][CH2:24][CH:23]([NH:26][C:2]3[CH:3]=[N:4][CH:5]=[N:6][CH:7]=3)[CH2:22][CH2:21]2)[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
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참가 물질

8

반응물 4

HCID 783445-Bromopyrimidine2회HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 86594093HCID 86594093, 화합물

생성물 1

HCID 69550769HCID 69550769, 화합물수율 20.6%

시약·촉매·용매 3

HCID 1140Toluene
용매
HCID 3283Diethyl Ether용매
HCID 8857Ethyl Acetate용매

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온도
70 °C

실험 절차

The title compound, MS (ISP): m/e=446.4 (M+H+), was prepared as for example 209, steps (A) to (C). Step (B) was performed using 5-bromo-pyrimidine as follows: A suspension of (+/−)-[cis-1-(2-phenyl-cyclohexyl)-piperidin-4-yl]-amine (1.46 g, 5.65 mmol) in toluene (35 ml) was degassed with a flow of argon for 10 minutes. Tris-(dibenzylideneacetone)dipalladium chloroform complex (179 mg, 0.17 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphtyl (BINAP, 108.0 mg, 0.17 mmol), sodium tert-butoxide (0.660 g, 6.87 mmol) and 5-bromopyrimidine (0.720 g, 4.53 mmol) were added under argon. The flask was sealed and warmed to 70° C. for 3 hours. The mixture was diluted with ethyl acetate (30 ml) and diethyl ether (30 ml) and washed three times with saturated sodium chloride solution. The organic phase was dried with sodium sulphate and evaporated, yielding a red oil. Purification was achieved by flash chromatography (dichloromethane/methanol/25% NH3 90:10:1). (+/−)-[cis-1-(2-Phenyl-cyclohexyl)-piperidin-4-yl]-pyrimidin-5-yl-amine (0.392 g, 20.6%) was obtained as an orange foam, MS (ISP): m/e=337.3 (M+H+). This was reacted with 5-methyl-isoxazole-3-carbonyl chloride in step (C).

후처리

  1. customwas degassed with a flow of argon for 10 minutes
  2. customThe flask was sealed
  3. washwashed three times with saturated sodium chloride solution
  4. dry with materialThe organic phase was dried with sodium sulphate
  5. customevaporated
  6. customyielding a red oil
  7. customPurification

출처 및 근거

ORD 기록
ord-d18e491d2554494ea6062524c570b7dd
출처 데이터셋
uspto-grants-2007_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07176316B2

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