Nitrogen → N-(5-Cyclopropyl-1H-pyrazol-3-yl)-N-(4-fluorobenzyl)pyridine-2,6-diamine

HRID 75885

반응식

HRID 75885 반응식
C1(C2C=CC=CC=2)C=CC=CC=1C(P(C)C)P(C)C.CC(C)([O-])C.[Na+].N#N.F[C:29]1[CH:30]=[C:31](CNC(=O)C)[C:32]([NH:45][C@H:46]([C:48]2[CH:53]=[CH:52][C:51]([F:54])=[CH:50][CH:49]=2)C)=[N:33][C:34]=1[NH:35]C1C=C(OC(C)C)NN=1.[CH:60]1([C:63]2[NH:67][N:66]=[C:65](N)[CH:64]=2)[CH2:62][CH2:61]1>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:60]1([C:63]2[NH:67][N:66]=[C:65]([N:45]([CH2:46][C:48]3[CH:49]=[CH:50][C:51]([F:54])=[CH:52][CH:53]=3)[C:32]3[CH:31]=[CH:30][CH:29]=[C:34]([NH2:35])[N:33]=3)[CH:64]=2)[CH2:62][CH2:61]1

참가 물질

8

반응물 5

HCID 947NitrogenHCID 27580143-cyclopropyl-1H-pyrazol-5-amineHCID 23676156Sodium t-butoxideHCID 86620606(Biphenyl-2-ylmethylene)bis(dimethylphosphine)HCID 178474560HCID 178474560, 화합물

생성물 1

HCID 67455889N-(5-Cyclopropyl-1H-pyrazol-3-yl)-N-(4-fluorobenzyl)pyridine-2,6-diamine수율 2%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매

반응 조건

온도
110 °C

실험 절차

To a flask was added Pd(OAc)2 (22.4 mg, 0.1 mmol), (biphenyl-2-ylmethylene)bis(dimethylphosphine) (60 mg, 0.2 mmol) and sodium tert-butoxide (240 mg, 2.5 mmol). The flask was sealed and refilled with N2. To the mixture was added a solution of 6-bromo-N-(4-fluorobenzyl)pyridin-2-amine (Method 19; 281 mg, 1.0 mmol) and 5-cyclopropyl-1H-pyrazol-3-amine (123 mg, 1.0 mmol) in toluene (5 ml). The reaction mixture was heated at 110° C. overnight. The solvent was removed and EtOAc was added and the mixture was washed with brine and was concentrated. Semi-prep HPLC (Gilson) purification gave the title compound (6.4 mg, 2%). 1H NMR (CDCl3) δ 0.65 (m, 2H), 0.95 (m, 2H), 1.80 (m, 1H), 4.43 (m, 2H), 4.91 (br s, 1H), 5.60 (br s, 1H), 5.80 (m, 1H), 6.18 (m, 1H), 6.73 (m, 1H), 7.00 (m, 2H), 7.25 (m, 3H).

후처리

  1. customThe flask was sealed
  2. customThe solvent was removed
  3. additionEtOAc was added
  4. washthe mixture was washed with brine
  5. concentrationwas concentrated
  6. customSemi-prep HPLC (Gilson) purification

출처 및 근거

ORD 기록
ord-c3771b5e94e54cc7bdf505e9ee9a9c55
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08835465B2

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