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Sodium Carbonate → (1R,2R)-2-((6-((6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol

HRID 1848003
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HRID 1848003 반응식
Br[C:2]1[CH:3]=[C:4]2[N:10]=[CH:9][N:8]([CH2:11][C:12]3[CH:28]=[CH:27][C:15]4[N:16]=[C:17]([NH:19][C@@H:20]5[CH2:25][CH2:24][CH2:23][CH2:22][C@H:21]5[OH:26])[S:18][C:14]=4[CH:13]=3)[C:5]2=[N:6][CH:7]=1.[CH3:29][N:30]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=[N:31]1.C([O-])([O-])=O.[Na+].[Na+]>C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.COCCOC>[CH3:29][N:30]1[CH:34]=[C:33]([C:2]2[CH:3]=[C:4]3[N:10]=[CH:9][N:8]([CH2:11][C:12]4[CH:28]=[CH:27][C:15]5[N:16]=[C:17]([NH:19][C@@H:20]6[CH2:25][CH2:24][CH2:23][CH2:22][C@H:21]6[OH:26])[S:18][C:14]=5[CH:13]=4)[C:5]3=[N:6][CH:7]=2)[CH:32]=[N:31]1
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참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86681028(1R,2R)-2-((6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol

생성물 1

HCID 71550132(1R,2R)-2-((6-((6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol수율 41%

시약·촉매·용매 2

HCID 178419050HCID 178419050, 화합물촉매
HCID 80711,2-Dimethoxyethane용매

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온도
100 °C

실험 절차

A stirred mixture of (1R,2R)-2-((6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol from Example 29 (80 mg, 0.175 mmol), 1-methylpyrazole-4-boronic acid pinacol ester (73 mg, 0.351 mmol), 2M aq Na2CO3 (400 μL, 0.40 mmol), and anhydrous DME (1.5 mL) was degassed under argon for 15 min. Bis(triphenylphosphine)palladium (II) dichloride (12 mg, 0.0171 mmol) was added and the reaction vessel was sealed and the mixture was heated at 100° C. for 15 h. After cooling to rt, the mixture was purified directly by reverse-phase HPLC using a mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Varian Pursuit XRs diphenyl column as the stationary phase to afford (1R,2R)-2-((6-((6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (33 mg, 41%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.64 (d, J=1.9 Hz, 1H), 8.56 (s, 1H), 8.26 (d, J=1.9 Hz, 1H), 8.23 (s, 1H), 7.95-8.01 (m, 2H), 7.67 (d, J=1.1 Hz, 1H), 7.20-7.32 (m, 2H), 5.47 (s, 2H), 4.76 (br s, 1H), 3.88 (s, 3H), 3.51 (m, 1H), 3.35 (m, 1H), 2.03 (m, 1H), 1.90 (m, 1H), 1.62 (d, J=4.7 Hz, 2H), 1.10-1.33 (m, 4H). LCMS (ESI) m/z 460 (M+H)+.

후처리

  1. customwas degassed under argon for 15 min
  2. customthe reaction vessel was sealed
  3. temperatureAfter cooling to rt
  4. customthe mixture was purified directly by reverse-phase
  5. additiona mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Varian Pursuit XRs diphenyl column as the stationary phase

출처 및 근거

ORD 기록
ord-fcc75b54f9b743e7b08b4d07d3450170
출처 데이터셋
uspto-grants-2015_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08952058B2

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