Sodium Carbonate → (2S)-1-(4-(1-isopropyl-3-(5-methyl-6-(methylamino)pyridin-3-yl)-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol

HRID 500718노트

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HRID 500718 반응식
I[C:2]1[C:6]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][C@@H:15]([OH:17])[CH3:16])[N:8]=2)=[CH:5][N:4]([CH:18]([CH3:20])[CH3:19])[N:3]=1.[CH3:21][NH:22][C:23]1[C:28]([CH3:29])=[CH:27][C:26](B2OC(C)(C)C(C)(C)O2)=[CH:25][N:24]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCO.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>[CH:18]([N:4]1[CH:5]=[C:6]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][C@@H:15]([OH:17])[CH3:16])[N:8]=2)[C:2]([C:26]2[CH:25]=[N:24][C:23]([NH:22][CH3:21])=[C:28]([CH3:29])[CH:27]=2)=[N:3]1)([CH3:20])[CH3:19]

참가 물질

7

반응물 3

HCID 10340Sodium CarbonateHCID 57416512N,3-Dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)pyridin-2-amineHCID 57856239(2S)-1-(4-(3-iodo-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol

생성물 1

HCID 25181760(2S)-1-(4-(1-isopropyl-3-(5-methyl-6-(methylamino)pyridin-3-yl)-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol수율 17%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 702Ethanol용매HCID 1140Toluene용매

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온도
85 °C

실험 절차

To a solution of (2S)-1-(4-(3-iodo-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol (B-1-3) (1 g, 2.58 mmol) in toluene (30 mL) and EtOH (10 mL) were added N,3-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (B-4-3) (2 g, 6.3 mmol in theory) and 2 N aq. Na2CO3 (4 mL). The resulting mixture was degassed under N2 for 2 minutes. Then Pd(PPh3)4 (0.3 g, 0.26 mmol) was added and the mixture was degassed again. The reaction was heated to 80-90° C. and stirred overnight. MS showed the reaction was complete and the mixture was cooled. The organic layer was separated and concentrated. The residue was purified by prep. HPLC to afford (2S)-1-(4-(1-isopropyl-3-(5-methyl-6-(methylamino)pyridin-3-yl)-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ol (B-4) (0.167 g, 16.98%) as a light yellow solid.

후처리

  1. customThe resulting mixture was degassed under N2 for 2 minutes
  2. customthe mixture was degassed again
  3. temperaturethe mixture was cooled
  4. customThe organic layer was separated
  5. concentrationconcentrated
  6. customThe residue was purified by prep

출처 및 근거

ORD 기록
ord-fe1c12ddddec40f6a097625b6a29b2db
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07772246B2

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