Hydrochloric Acid → 5-(1-Piperidin-4-yl-1H-pyrazol-4-yl)-3-(4-trifluoromethylbenzothiazol-2-yl)-pyridin-2-ylamine

HRID 1926393ノート

反応式

HRID 1926393 の反応式
C(OC([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)(C)(C)C.Cl[C:36]1[S:37][C:38]2[CH:44]=[CH:43][CH:42]=[C:41]([C:45]([F:48])([F:47])[F:46])[C:39]=2[N:40]=1.C(=O)([O-])[O-].[K+].[K+].Cl>COCCOC.O.C(Cl)Cl.C(OCC)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH:8]1[CH2:9][CH2:10][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:24]=[C:23]([C:36]4[S:37][C:38]5[CH:44]=[CH:43][CH:42]=[C:41]([C:45]([F:48])([F:47])[F:46])[C:39]=5[N:40]=4)[C:22]([NH2:34])=[N:21][CH:20]=3)[CH:16]=[N:15]2)[CH2:12][CH2:13]1

参加物

10

反応物 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 247289502-Chloro-4-(trifluoromethyl)-1,3-benzothiazoleHCID 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 ester

生成物 1

HCID 675208855-(1-Piperidin-4-yl-1H-pyrazol-4-yl)-3-(4-trifluoromethylbenzothiazol-2-yl)-pyridin-2-ylamine

試薬・触媒・溶媒 5

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 3283Diethyl Ether溶媒HCID 6344Dichloromethane溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
100 °C

実験手順

A mixture 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 (BB8) (75 mg, 0.16 mmol), 2-chloro-4-trifluoromethyl-1,3-benzothiazole (46 mg, 0.19 mmol), potassium carbonate (66 mg, 0.48 mmol), Pd(PPh3)4 (18 mg, 0.016 mmol) in DME (3 mL) and H2O (1 mL) was evacuated and refilled with N2 (3×), then it was heated at 100° C. for 30 min in the microwave reactor. The mixture was diluted with EtOAc (30 mL), washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (Hex.:EtOAc=30:70→15:85) to give a yellow solid. This material was dissolved in DCM (2 mL) and treated with 1M HCl in diethyl ether (3 mL). The resulting mixture was stirred at room temperature overnight. The title compound was collected by filtration as a yellow solid and washed with DCM. MS (ES+): m/z=445.10 [MH+].

後処理

  1. customwas evacuated
  2. additionrefilled with N2 (3×)
  3. additionThe mixture was diluted with EtOAc (30 mL)
  4. washwashed with brine (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel chromatography (Hex.:EtOAc=30:70→15:85)
  9. customto give a yellow solid
  10. filtrationThe title compound was collected by filtration as a yellow solid
  11. washwashed with DCM

出典と根拠

ORDレコード
ord-238446c660f14fcda49e231fc9d64b1e
出典データセット
uspto-grants-2012_05
特許番号
US08178668B2

反応ノート

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