Sodium Carbonate → (R)-2'-bromo-7'-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine

HRID 1472451노트

반응식

HRID 1472451 반응식
C(=O)([O-])[O-].[Na+].[Na+].[F:7][C:8]1[CH:13]=[C:12](B(O)O)[CH:11]=[CH:10][N:9]=1.[Br:17][C:18]1[CH:31]=[CH:30][C:29]2[O:28][C:27]3[C:22](=[CH:23][C:24](I)=[CH:25][CH:26]=3)[C@@:21]3([N:37]=[C:36]([NH2:38])[CH2:35][O:34][CH2:33]3)[C:20]=2[CH:19]=1>COCCOC.O.[Cl-].[Na+].O.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>[Br:17][C:18]1[CH:31]=[CH:30][C:29]2[O:28][C:27]3[C:22](=[CH:23][C:24]([C:12]4[CH:11]=[CH:10][N:9]=[C:8]([F:7])[CH:13]=4)=[CH:25][CH:26]=3)[C@@:21]3([N:37]=[C:36]([NH2:38])[CH2:35][O:34][CH2:33]3)[C:20]=2[CH:19]=1

참가 물질

8

반응물 3

HCID 10340Sodium CarbonateHCID 27833962-Fluoropyridine-4-boronic acidHCID 58465890(S)-2'-bromo-7'-iodo-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine

생성물 1

HCID 67438537(R)-2'-bromo-7'-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매HCID 57417360Sodium chloride; water용매

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온도
80 °C

실험 절차

In a microwave vial, sodium carbonate (0.094 g, 0.885 mmol), 2-fluoropyridin-4-ylboronic acid (0.048 g, 0.339 mmol), Pd(PPh3)4 (0.034 g, 0.030 mmol), and (S)-2′-bromo-7′-iodo-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (0.139 g, 0.295 mmol) were suspended in DME (2.5 mL) and water (0.5 mL). Argon gas was blown through the vessel which was sealed and heated in an 80° C. oil bath. After 6 h, the reaction mixture was diluted with brine (10 mL) and the aqueous phase was extracted with 7.5% MeOH-dcm (3×25 mL). The organics were combined, washed with dilute brine (5 mL), dried over sodium sulfate and concentrated. The material was purified through silica gel (33 mL) using 3.5 to 4.5 to 7% MeOH-DCM to afford (R)-2′-bromo-7′-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine Step 2: In a microwave vial, the potassium phosphate (0.071 g, 0.334 mmol), PdCl2(AmPhos)2 (7.88 mg, 0.011 mmol), 2-fluoropyridin-3-ylboronic acid (0.020 g, 0.139 mmol), and (R)-2′-bromo-7′-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (0.049 g, 0.111 mmol) were suspended in dioxane (2 mL) and water (0.5 mL). Argon gas was blown through the vessel, which was sealed and heated by microwave at 120° C. for 30 min. The mixture was concentrated, and the residue was diluted with brine (15 mL), and the aqueous phase was extracted with 5% MeOH-dcm (3×25 mL). The organics were combined, dried over sodium sulfate and concentrated. The residue was purified by chromatography (3.5%-4.5% MeOH/DCM) to afford (R)-2′-(2-fluoropyridin-3-yl)-7′-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (35 mg, 0.076 mmol). MS (m/z) 457 (M+H)+.

후처리

  1. customwas sealed
  2. extractionthe aqueous phase was extracted with 7.5% MeOH-dcm (3×25 mL)
  3. washwashed with dilute brine (5 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe material was purified through silica gel (33 mL)

출처 및 근거

ORD 기록
ord-e123b680207342fa96f0daa696b5f893
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09012446B2

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