4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → 5-[5-(1H-Pyrazol-4-yl)-imidazo[1,2-a]pyrazin-8-ylamino]-pyridine-2-carboxylic acid (2-diethylamino-ethyl)-amide

HRID 1366127노트

반응식

HRID 1366127 반응식
N1(C2C=CC(NC3C4N(C=CN=4)C(C4C=CNC(=O)C=4)=CN=3)=CC=2)CCOCC1.[CH2:30]([N:32]([CH2:55][CH3:56])[CH2:33][CH2:34][NH:35][C:36]([C:38]1[CH:43]=[CH:42][C:41]([NH:44][C:45]2[C:46]3[N:47]([CH:52]=[CH:53][N:54]=3)[C:48](Br)=[CH:49][N:50]=2)=[CH:40][N:39]=1)=[O:37])[CH3:31].CC1(C)C(C)(C)OB([C:65]2[CH:66]=[N:67][NH:68][CH:69]=2)O1.CC([O-])(C)C.[Na+]>CN(C=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:30]([N:32]([CH2:55][CH3:56])[CH2:33][CH2:34][NH:35][C:36]([C:38]1[CH:43]=[CH:42][C:41]([NH:44][C:45]2[C:46]3[N:47]([CH:52]=[CH:53][N:54]=3)[C:48]([C:65]3[CH:66]=[N:67][NH:68][CH:69]=3)=[CH:49][N:50]=2)=[CH:40][N:39]=1)=[O:37])[CH3:31]

참가 물질

7

반응물 4

HCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 23676156Sodium t-butoxideHCID 248574474-[8-(4-Morpholin-4-yl-phenylamino)imidazo[1,2-a]pyrazin-5-yl]-1H-pyridin-2-oneHCID 590231155-(5-Bromo-imidazo[1,2-a]pyrazin-8-ylamino)-pyridine-2-carboxylic acid (2-diethylamino-ethyl)-amide

생성물 1

HCID 590231145-[5-(1H-Pyrazol-4-yl)-imidazo[1,2-a]pyrazin-8-ylamino]-pyridine-2-carboxylic acid (2-diethylamino-ethyl)-amide수율 18.3%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 21962138N,N-Dimethylformamide--water (1/1)용매

실험 절차

In the same way as described for Compound 85, step 1, using 5-(5-bromo-imidazo[1,2-a]pyrazin-8-ylamino)-pyridine-2-carboxylic acid (2-diethylamino-ethyl)-amide (169 mg, 0.39 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (91 mg, 0.47 mmol), Pd(PPh3)4 (45 mg, 0.039 mmol) and NaOtBu (150 mg, 1.56 mmol) in DMF:water (3:1, 9 mL). The crude residue is purified by reverse phase preparative HPLC to give the title compound (30 mg, 18%). LCMS: Rt 1.81 min (97.6%); m/z (APCI) 420 (M+H)+; 1H-NMR (400 MHz, d6-DMSO) δ (ppm). 1.02 (6H, t), 2.36-2.71 (4H, m), 3.09-3.40 (4H, m), 7.73 (1H, s), 7.84 (1H, s), 8.04 (1H, d), 8.24 (3H, m), 8.56 (1H, m), 8.79 (1H, d), 9.28 (1H, s), 10.24 (1H, s), 13.40 (1H, br s).

후처리

  1. customThe crude residue is purified by reverse phase preparative HPLC

출처 및 근거

ORD 기록
ord-783a23424777469e886f84ad9420225c
출처 데이터셋
uspto-grants-2011_02
특허 번호
US07893058B2

반응 노트

불러오는 중…