Potassium Phosphate, Tribasic → Tert-butyl 4-(6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzylcarbamate

HRID 870657ノート

反応式

HRID 870657 の反応式
Br[C:2]1[N:6]2[N:7]=[C:8]([NH:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[F:16][C:17]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[CH:28][C:18]=1[CH2:19][NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(#N)C.O>[CH2:12]([NH:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([C:30]3[CH:29]=[CH:28][C:18]([CH2:19][NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:24])[CH3:25])=[C:17]([F:16])[CH:31]=3)=[CH:3][N:4]=2)[N:7]=1)[CH2:13][CH2:14][CH3:15]

参加物

6

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 669802924-(n-Boc-aminomethyl)-3-fluorobenzeneboronic acid pinacol esterHCID 866963223-Bromo-6-(butylamino)imidazo[1,2-b]pyridazine

生成物 1

HCID 86696354Tert-butyl 4-(6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzylcarbamate収率 38%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 18373917Acetonitrile--water (1/1)溶媒

反応条件

温度
145 °C

実験手順

To a mixture of 3-bromo-N-butylimidazo[1,2-b]pyridazin-6-amine (187 mg, 0.7 mmol), tert-butyl 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzylcarbamate (293 mg, 1.2 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (24 mg, 0.034 mmol) and tripotassium phosphate (144 mg, 1.04 mmol) was added 3:1 acetonitrile/water (3 mL). The resulting mixture was heated at 145° C. (microwave) for 800 s. The reaction was then filtered and concentrated. The residue was dissolved in methanol, and then filtered again. The filtration was finally purified by preparative HPLC (neutral) to afford tert-butyl 4-(6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzylcarbamate (110 mg, 38% yield) as a white solid: 1H NMR (CHLOROFORM-d) δ: 8.02 (dd, J=11.9, 1.3 Hz, 1H), 7.78-7.89 (m, 2H), 7.74 (d, J=9.6 Hz, 1H), 7.43 (t, J=8.0 Hz, 1H), 7.28 (s, 2H), 6.52 (d, J=9.6 Hz, 1H), 4.95 (br. s., 1H), 4.31-4.57 (m, 3H), 3.45 (td, J=7.1, 5.6 Hz, 2H), 1.68-1.80 (m, 2H), 1.02 (t, J=7.3 Hz, 3H); LRMS (ESI) m/e 414.3 [(M+H)+, calcd for C22H29FN5O2 414.2].

後処理

  1. filtrationThe reaction was then filtered
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in methanol
  4. filtrationfiltered again
  5. filtrationThe filtration
  6. customwas finally purified by preparative HPLC (neutral)

出典と根拠

ORDレコード
ord-08773336cd8d48a1a9c43f4eb4a3b260
出典データセット
uspto-grants-2015_03
特許番号
US08969565B2

反応ノート

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