Potassium Carbonate → 4-{4-[5-(2-Amino-pyrimidin-5-yl)-imidazo[2,1-b][1,3,4]thiadiazol-2-yl]-2-methoxy-phenoxy}-piperidine-1-carboxylic acid tert-butyl ester

HRID 2409548노트

반응식

HRID 2409548 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[S:25][C:24]4=[N:26][CH:27]=[C:28](I)[N:23]4[N:22]=3)=[CH:17][C:16]=2[O:30][CH3:31])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:32][C:33]1[N:38]=[CH:37][C:36](B2OC(C)(C)C(C)(C)O2)=[CH:35][N:34]=1.O1CCOCC1.C([O-])([O-])=O.[K+].[K+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[S:25][C:24]4=[N:26][CH:27]=[C:28]([C:36]5[CH:35]=[N:34][C:33]([NH2:32])=[N:38][CH:37]=5)[N:23]4[N:22]=3)=[CH:17][C:16]=2[O:30][CH3:31])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

7

반응물 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 667168474-[4-(5-Iodo-imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-2-methoxy-phenoxy]-piperidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 667172554-{4-[5-(2-Amino-pyrimidin-5-yl)-imidazo[2,1-b][1,3,4]thiadiazol-2-yl]-2-methoxy-phenoxy}-piperidine-1-carboxylic acid tert-butyl ester수율 14.3%

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매

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온도
120 °C

실험 절차

A mixture of 4-[4-(5-iodo-imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-2-methoxy-phenoxy]-piperidine-1-carboxylic acid tert-butyl ester (82 mg, 0.147 mmol, 1 eq), 2-aminopyrimidine-5-boronic acid pinacol ester (48 mg, 0.22 mmol, 1.5 eq), 1,4-dioxane (4 mL), K2CO3 (61 mg, 0.441 mmol, 3 eq), H2O (1.6 ml) and Pd(PPh3)2Cl2 (10 mg, 0.0147 mmol, 0.1 eq) was heated under microwave irradiation (120° C., 30 min). Solvents were removed and the residue was purified in an Isolute Flash Si II column (0-3% MeOH in DCM). The product obtained was triturated with EtOAc and filtered. The filtrate was evaporated and the residue was triturated with acetone. The filtrate was evaporated. The residue was purified by column chromatography (EtOAc) to give the desired product (11 mg, 14%). HPLC-MS (5-100% B in 8 min at 0.8 mL): tR=5.90 min, [M+H]+ m/z 524.2; 1H NMR (300 MHz, CDCl3) δ 8.86 (s, 2H), 7.43 (m, 2H), 7.36 (dd, J=8.3, 2.1 Hz, 1H), 6.96 (d, J=8.4 Hz, 1H), 5.26 (s, 2H), 4.53 (m, 1H), 3.93 (s, 3H), 3.75 (m, 2H), 3.29 (m, 2H), 1.93 (m, 2H), 1.81 (m, 2H), 1.45 (s, 9H).

후처리

  1. customSolvents were removed
  2. customthe residue was purified in an Isolute Flash Si II column (0-3% MeOH in DCM)
  3. customThe product obtained
  4. customwas triturated with EtOAc
  5. filtrationfiltered
  6. customThe filtrate was evaporated
  7. customthe residue was triturated with acetone
  8. customThe filtrate was evaporated
  9. customThe residue was purified by column chromatography (EtOAc)

출처 및 근거

ORD 기록
ord-3126e55eafa243e2913c7658b95679a6
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08815918B2

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