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

HRID 1844369ノート

反応式

HRID 1844369 の反応式
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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

実験手順

(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.

後処理

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

出典と根拠

ORDレコード
ord-a598491aca1c4a69a73acca59576b3cd
出典データセット
uspto-grants-2015_02
特許番号
US08946415B2

反応ノート

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