Water → HCID 67521098, 화합물

HRID 1926237노트

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HRID 1926237 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[N:21][C:22]([NH2:34])=[C:23](B4OC(C)(C)C(C)(C)O4)[CH:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:35][C:36]1[CH:37]=[C:38]2[C:43](=[CH:44][CH:45]=1)[CH:42]=[N:41][C:40](OS(C(F)(F)F)(=O)=O)=[CH:39]2.O1CCOCC1.C([O-])([O-])=O.[Cs+].[Cs+].O>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[N:21][C:22]([NH2:34])=[C:23]([C:40]4[N:41]=[CH:42][C:43]5[C:38]([CH:39]=4)=[CH:37][C:36]([CH3:35])=[CH:45][CH:44]=5)[CH:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

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7

반응물 5

HCID 962WaterHCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 534879604-[4-[6-Amino-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridin-3-yl]pyrazol-1-yl]piperidine-1-carboxylic acid tert-butyl esterHCID 86633134HCID 86633134, 화합물

생성물 1

HCID 67521098HCID 67521098, 화합물

시약·촉매·용매 1

HCID 15220664Palladium--triphenylphosphane (1/1)촉매

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온도
105 °C

실험 절차

To a solution of 4-{4-[6-amino-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (BB3) (53.7 mg, 0.114 mmol), trifluoromethanesulfonic acid 6-methylisoquinolin-3-yl ester (35.0 mg, 0.120 mmol), and PS-PPh3-Pd (0.10 mmol/g loading; 76 mg, 0.0076 mmol; Argonaut) in 1,4-dioxane (2.0 mL, 25 mmol) in a sealable microwave tube was added a solution of Cs2CO3 (75.6 mg, 0.232 mmol) in H2O (0.60 mL, 33 mmol). The tube was sealed, evacuated and refilled with nitrogen (3×), and heated in the microwave reactor to 105° C. for 30 minutes. The resin was filtered off and washed with DCM. The combined filtrate and washings were washed with 1M NaOH, water and brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by preparative TLC [20×20 cm plate, 500 μm layer of silica gel, eluting with 3.5% MeOH in DCM (3×)]. Material from the main band was collected and dried in vacuo overnight to give the title compound as a yellow glassy solid. 1H NMR (400 MHz, CDCl3): δ=9.22 (s, 1H), 8.26 (d, J=2.0 Hz, 1H), 7.94 (s, 1H), 7.93 (d, J=2.0 Hz, 1H), 7.91 (d, J=8.4 Hz, 1H), 7.77 (d, J=0.4 Hz, 1H), 7.67 (brs, 1H), 7.66 (s, 1H), 7.46 (dd, J=8.4, 1.6 Hz, 1H), 6.43 (brs, 2H), 4.38-4.19 (m, 3H), 2.92 (brt, J=11.0 Hz, 2H), 2.58 (s, 3H), 2.19 (brdd, J=2.0, 12.4 Hz, 2H), 1.98 (dq, J=4.4, 12.0 Hz, 2H), 1.49 (s, 9H). MS(ES+): m/z=485.19 (100) [MH+], 429.13 (7) [MH+-isobutene]. HPLC: tR=2.71 min (polar—5 min, ZQ2).

후처리

  1. customThe tube was sealed
  2. customevacuated
  3. additionrefilled with nitrogen (3×)
  4. filtrationThe resin was filtered off
  5. washwashed with DCM
  6. washThe combined filtrate and washings were washed with 1M NaOH, water and brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by preparative TLC [20×20 cm plate, 500 μm layer of silica gel, eluting with 3.5% MeOH in DCM (3×)]
  11. customMaterial from the main band was collected
  12. customdried in vacuo overnight

출처 및 근거

ORD 기록
ord-49ec28f676f54958ad129d90e30f75a5
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08178668B2

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