Triethylamine → (R)-tetrahydrofuran-3-yl-4-(3-(5-fluoro-2-methoxypyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)piperazine-1-carboxylate

HRID 1844369노트

반응식

HRID 1844369 반응식
Br[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([N:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C@@H:20]4[CH2:24][CH2:23][O:22][CH2:21]4)=[O:18])[CH2:13][CH2:12]3)=[N:7][C:6]=12.[F:25][C:26]1[CH:27]=[C:28](B2OC(C)(C)C(C)(C)O2)[C:29]([O:32][CH3:33])=[N:30][CH:31]=1.C(N(CC)CC)C.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2].O>[O:22]1[CH2:23][CH2:24][C@@H:20]([O:19][C:17]([N:14]2[CH2:15][CH2:16][N:11]([C:8]3[CH:9]=[CH:10][N:5]4[N:4]=[CH:3][C:2]([C:28]5[C:29]([O:32][CH3:33])=[N:30][CH:31]=[C:26]([F:25])[CH:27]=5)=[C:6]4[N:7]=3)[CH2:12][CH2:13]2)=[O:18])[CH2:21]1

참가 물질

8

반응물 4

HCID 8471TriethylamineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 467397215-Fluoro-2-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 86697452(R)-tetrahydrofuran-3-yl 4-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)piperazine-1-carboxylate

생성물 1

HCID 86697455(R)-tetrahydrofuran-3-yl-4-(3-(5-fluoro-2-methoxypyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)piperazine-1-carboxylate수율 27.1%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

(R)-tetrahydrofuran-3-yl 4-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)piperazine-1-carboxylate (100 mg, 0.25 mmol), 5-fluoro-2-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (127 mg, 0.5 mmol), triethylamine (211 uL, 1.5 mmol), Pd(OAc)2 (1 mg, 0.0025 mmol), and x-Phos (5 mg, 0.005 mmol) were taken up in 4 mL dioxane and 1 mL water under nitrogen and stirred at 85° C. for 2 hours. Reaction then cooled to room temperature, filtered through celite plug with acetonitrile and DCM. Reduced in vacuo and purified on Shimadzu neutral phase prep, lypholized to get 30 mg product. 1H NMR (400 MHz, DMSO-d6) δ 8.80 (d, J=7.83 Hz, 1H), 8.72 (dd, J=3.03, 10.36 Hz, 1H), 8.56 (s, 1H), 7.94 (d, J=3.03 Hz, 1H), 6.86 (d, J=7.83 Hz, 1H), 5.18 (d, J=1.77 Hz, 1H), 4.00 (s, 3H), 3.71-3.83 (m, 8H), 3.32 (s, 2H), 2.08 (s, 1H), 2.13 (s, 1H), 1.89-2.00 (m, 1H) LRMS (ESI) m/z 443 [(M+H)]+, calc'd for C21H23FN6O4: 442.45.

후처리

  1. customReaction
  2. filtrationfiltered through celite plug with acetonitrile and DCM
  3. custompurified on Shimadzu neutral phase prep

출처 및 근거

ORD 기록
ord-a598491aca1c4a69a73acca59576b3cd
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946415B2

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