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Dimethylformamide → 6-[(4-{3-cyano-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propyl}piperazin-1-yl)carbonyl]-5-fluoronicotinonitrile

HRID 1772798
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인쇄 미리보기

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HRID 1772798 반응식
Cl[C:2]1[CH:3]=[C:4]([F:35])[C:5]([C:8]([N:10]2[CH2:15][CH2:14][N:13]([CH2:16][CH:17]([N:21]3[CH:25]=[C:24]([C:26]4[C:27]5[CH:34]=[CH:33][NH:32][C:28]=5[N:29]=[CH:30][N:31]=4)[CH:23]=[N:22]3)[CH2:18][C:19]#[N:20])[CH2:12][CH2:11]2)=[O:9])=[N:6][CH:7]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.[CH3:65][N:66](C=O)C>O.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.[Pd].[Pd].[C-]#N.[Zn+2].[C-]#N>[C:19]([CH2:18][CH:17]([N:21]1[CH:25]=[C:24]([C:26]2[C:27]3[CH:34]=[CH:33][NH:32][C:28]=3[N:29]=[CH:30][N:31]=2)[CH:23]=[N:22]1)[CH2:16][N:13]1[CH2:14][CH2:15][N:10]([C:8]([C:5]2[C:4]([F:35])=[CH:3][C:2]([C:65]#[N:66])=[CH:7][N:6]=2)=[O:9])[CH2:11][CH2:12]1)#[N:20]
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 3

HCID 6228DimethylformamideHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 509960004-{4-[(5-chloro-3-fluoropyridin-2-yl)carbonyl]piperazin-1-yl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile

생성물 1

HCID 509960016-[(4-{3-cyano-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propyl}piperazin-1-yl)carbonyl]-5-fluoronicotinonitrile

시약·촉매·용매 3

HCID 962
Water
촉매
HCID 11186Zinc cyanide (Zn(CN)2)촉매
HCID 9811564Bis(dibenzylideneacetone)palladium촉매

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온도
150 °C

실험 절차

A mixture of 4-{4-[(5-chloro-3-fluoropyridin-2-yl)carbonyl]piperazin-1-yl}-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile (15 mg, 0.030 mmol, from Example 1), 2-(Dicyclohexylphosphino)-2′,6′-dimethoxy-1,1′-biphenyl (3.7 mg, 0.0091 mmol), Tris(dibenzylideneacetone)dipalladium(0) (3.3 mg, 0.0036 mmol) and zinc cyanide (18 mg, 0.15 mmol) in DMF (0.50 mL, 6.4 mmol) and one drop of water was degassed by purging with a stream of nitrogen for 5 minutes, then was heated in the microwave for 15 minutes at 150° C. Preparative HPLC-MS, eluting with a gradient of MeCN/H2O containing 0.15% NH4OH, was used to purify the product (6 mg, 40%). 1H NMR (300 MHz, d6-dmso): δ 12.10 (br s, 1H), 8.93 (t, 1H), 8.81 (s, 1H), 8.68 (s, 1H), 8.59 (dd, 1H), 8.37 (s, 1H), 7.60 (d, 1H), 6.97 (d, 1H), 4.98 (tt, 1H), 3.65-3.58 (m, 2H), 3.25-3.19 (m, 2H), 3.19-3.13 (m, 2H), 2.92-2.78 (m, 2H), 2.66-2.25 (m, 4H); LCMS (M+H)+: 485.2.

후처리

  1. customwas degassed
  2. customby purging with a stream of nitrogen for 5 minutes
  3. washPreparative HPLC-MS, eluting with a gradient of MeCN/H2O containing 0.15% NH4OH
  4. customto purify the product (6 mg, 40%)

출처 및 근거

ORD 기록
ord-63d362c19db94c958e38f9111e91a6ba
출처 데이터셋
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09249145B2

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