Nitrogen → HCID 69670585, 화합물

HRID 81074

반응식

HRID 81074 반응식
Cl[C:2]1[CH:9]=[C:8]([NH:10][NH2:11])[C:5]([C:6]#[N:7])=[C:4]([C:12]2[CH:17]=[CH:16][C:15]([O:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[CH:14][CH:13]=2)[N:3]=1.B([C:28]1[CH:36]=[CH:35][C:31]([C:32]([OH:34])=[O:33])=[C:30]([F:37])[CH:29]=1)(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].N#N>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[NH2:7][C:6]1[C:5]2[C:4]([C:12]3[CH:17]=[CH:16][C:15]([O:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:14][CH:13]=3)=[N:3][C:2]([C:28]3[CH:36]=[CH:35][C:31]([C:32]([OH:34])=[O:33])=[C:30]([F:37])[CH:29]=3)=[CH:9][C:8]=2[NH:10][N:11]=1

참가 물질

7

반응물 4

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 27632014-Carboxy-3-fluorophenylboronic acidHCID 86665697HCID 86665697, 화합물

생성물 1

HCID 69670585HCID 69670585, 화합물

시약·촉매·용매 2

HCID 178418807HCID 178418807, 화합물촉매HCID 6228Dimethylformamide용매

반응 조건

온도
85 °C

실험 절차

A solution of 6-chloro-4-hydrazinyl-2-(4-phenoxyphenyl)nicotinonitrile (9.5 mg, 0.028 mmol), 4-borono-2-fluorobenzoic acid (14.5 mg, 0.079 mmol), 2 M aqueous potassium phosphate (0.071 mL, 0.141 mmol) and PdCl2(dppf)-CH2Cl2 adduct (4.6 mg, 5.63 μmol) in DMF (0.45 mL) was degassed by vacuum-N2 refill cycle twice. The sealed tube was then heated at 85° C. under N2. After 1.5 h, no desired product was detected. Additional 4-borono-2-fluorobenzoic acid (21.4 mg), PdCl2(dppf)-CH2Cl2 adduct (11 mg), potassium phosphate (0.14 mL) and DMF (0.3 mL) were added. The mixture was again degassed by vacuum-N2 refill cycle twice and stirred at 85° C. for 20 h. The mixture was diluted with 1 N aqueous HCl (0.7 mL) and MeOH (0.8 mL), and purified by reverse phase HPLC (Sunfire S10 30×250 mm column), eluting with 60-90% solvent B (10% methanol-90% water-0.1% TFA) in solvent A (90% methanol-10% water-0.1% TFA), to give Example 245 as yellow powder (2.7 mg, 14% yield), assumed as bis-TFA salt. 1H NMR (400 MHz, methanol-d4) δ ppm 8.15 (1H, t, J=7.65 Hz), 7.89-7.93 (2H, m), 7.86 (1H, s), 7.77-7.84 (2H, m), 7.44-7.50 (2H, m), 7.24-7.30 (3H, m), 7.15-7.19 (2H, m); MS (ES+) m/z: 441.2 (M+H); LC retention time: 3.438 min (analytical HPLC Method A).

출처 및 근거

ORD 기록
ord-81e8e847c17a4d47869d596b2c235dbf
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846673B2

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