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Diisopropylethylamine → 1-(3-(2-Fluoropropan-2-yl)isoxazol-5-yl)-3-(3-(6-methoxy-7-(2-methoxyethoxy)quinazolin-4-ylthio)phenyl)urea

HRID 871599
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HRID 871599 반응식
[F:1][C:2]([C:5]1[CH:9]=[C:8]([NH:10][C:11](=[O:19])OC2C=CC=CC=2)[O:7][N:6]=1)([CH3:4])[CH3:3].[CH3:20][O:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][C:31]=1[O:32][CH2:33][CH2:34][O:35][CH3:36])[N:28]=[CH:27][N:26]=[C:25]2[S:37][C:38]1[CH:39]=[C:40]([CH:42]=[CH:43][CH:44]=1)[NH2:41].C(N(C(C)C)CC)(C)C>CN(C1C=CN=CC=1)C>[F:1][C:2]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:41][C:40]2[CH:42]=[CH:43][CH:44]=[C:38]([S:37][C:25]3[C:24]4[C:29](=[CH:30][C:31]([O:32][CH2:33][CH2:34][O:35][CH3:36])=[C:22]([O:21][CH3:20])[CH:23]=4)[N:28]=[CH:27][N:26]=3)[CH:39]=2)=[O:19])[O:7][N:6]=1)([CH3:3])[CH3:4]
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참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 66876626Phenyl 3-(2-fluoropropan-2-yl)isoxazol-5-ylcarbamateHCID 668767643-(6-Methoxy-7-(2-methoxyethoxy)quinazolin-4-ylthio)aniline

생성물 1

HCID 582679411-(3-(2-Fluoropropan-2-yl)isoxazol-5-yl)-3-(3-(6-methoxy-7-(2-methoxyethoxy)quinazolin-4-ylthio)phenyl)urea

시약·촉매·용매 1

HCID 14284
4-(Dimethylamino)pyridine
촉매

실험 절차

The procedure for Example 138B was used to react phenyl 3-(2-fluoropropan-2-yl)isoxazol-5-ylcarbamate from Example 42A (86 mg, 0.33 mmol) with 3-(6-methoxy-7-(2-methoxyethoxy)quinazolin-4-ylthio)aniline described in Example 231A (97 mg, 0.27 mmol). To this solution was added diisopropylethyl amine (71 μL, 0.41 mmol) and DMAP (5.0 mg, 0.04 mmol). The reaction was concentrated to dryness and partitioned between water and dichloromethane, and extracted twice. The combined extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. The oil was purified by silica gel chromatography eluting with ethyl acetate/dichloromethane 12-70% over 18 column volumes. The appropriate peak was concentrated to a white solid weighing 18 mg. 1H (DMSO-d6) 10.42 (s, 1H), 9.11 (s, 1H), 8.69 (s, 1H), 7.84 (s, 1H), 7.55 (m, 1H), 7.45 (m, 1H), 7.34 (m, 3H), 6.16 (s, 1H), 4.33 (m, 2H), 4.00 (s, 3H), 3.76 (s, 2H), 1.70 (s, 3H), 1.63 (s, 3H). LCMS (ESI) m/z 528 (M+H)

후처리

  1. concentrationThe reaction was concentrated to dryness
  2. custompartitioned between water and dichloromethane
  3. extractionextracted twice
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe oil was purified by silica gel chromatography
  9. washeluting with ethyl acetate/dichloromethane 12-70% over 18 column volumes
  10. concentrationThe appropriate peak was concentrated to a white solid

출처 및 근거

ORD 기록
ord-ff86f871ece94bf0a8f11364379af3ab
출처 데이터셋
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08969587B2

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