1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 57590616、化合物

HRID 732280

反応式

HRID 732280 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([NH2:28])[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1.[CH:29]1N=CN(C(N2C=NC=C2)=S)C=1.[F:41][C:42]([F:51])([F:50])[CH2:43][NH:44][CH2:45][CH:46]([OH:49])[CH2:47][OH:48].CCN=C=NCCCN(C)C.NC(N)=S>CN(C1C=CN=CC=1)C.O.ClCCCl.C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([N:28]=[C:29]4[N:44]([CH2:43][C:42]([F:50])([F:51])[F:41])[CH2:45][CH:46]([CH2:47][OH:48])[O:49]4)[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1

参加物

10

反応物 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide2 回HCID 802641,1'-ThiocarbonyldiimidazoleHCID 2723790ThioureaHCID 53630477Allitinib metabolite M62 回HCID 60632717HCID 60632717、化合物

生成物 1

HCID 57590616HCID 57590616、化合物収率 7%

試薬・触媒・溶媒 4

HCID 142844-(Dimethylamino)pyridine触媒HCID 111,2-Dichloroethane溶媒3 回HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
70 °C

実験手順

[2-{4-[3-Chloro-4-(3-fluoro-benzyloxy)-phenylamino]-quinazolin-6-ylimino}-3-(2,2,2-trifluoro-ethyl)-oxazolidin-5-yl]-methanol is prepared from N4-[3-chloro-4-(3-fluoro-benzyloxy)-phenyl]-quinazoline-4,6-diamine. 1,1-Thiocarbonyldiimidazole (55 mg, 0.28 mmol) is added to a solution of N4-[3-chloro-4-(3-fluoro-benzyloxy)-phenyl]-quinazoline-4,6-diamine (100 mg, 0.253 mmol) in 1:1 THF:DCE (1 ml). After 30 min, a 1:1 THF:DCE (1 ml) solution of 3-(2,2,2-trifluoro-ethylamino)-propane-1,2-diol (88 mg, 0.51 mmol) is added. After 16 h, the reaction mixture is concentrated and the resulting solid is suspended in Et2O and filtered. EDCI (110 mg, 0.560 mmol) and catalytic DMAP is added to a suspension of the solid thiourea in 1:1 THF:DCE (4 ml). After 6 h, an additional 200 mg EDCI is added and the reaction mixture is heated to 70° C. After 16 h, the reaction mixture is cooled to room temperature and diluted with water. The aqueous layer is extracted with EtOAc. The combined organic extracts are dried (Na2SO4) and concentrated. Purification on a silica gel column (EtOAc) yields the desired product as a yellow solid (10 mg, 7%). MS ESI (+) m/z 576.2, 578.2 (M+1) detected; 1H NMR (400 MHz, DMSO-d6) δ 9.56 (s, 1H), 8.47 (s, 1H), 8.08 (d, 1H), 7.94 (s, 1H), 7.77 (m, 1H), 7.62 (m, 2H), 7.47 (m, 1H), 7.32 (m, 2H), 7.24 (d, 1H) 7.19 (m, 1H), 5.25 (s, 2H), 5.19 (t, 1H), 4.77 (br, 1H), 3.77 (m, 1H), 3.66 (m, 1H), 3.55 (m, 2H), 2.97 (m, 2H).

後処理

  1. waitAfter 16 h
  2. concentrationthe reaction mixture is concentrated
  3. filtrationfiltered
  4. waitAfter 6 h
  5. waitAfter 16 h
  6. temperaturethe reaction mixture is cooled to room temperature
  7. extractionThe aqueous layer is extracted with EtOAc
  8. dry with materialThe combined organic extracts are dried (Na2SO4)
  9. concentrationconcentrated
  10. customPurification on a silica gel column (EtOAc)

出典と根拠

ORDレコード
ord-90b622b29a5c41cf8a14dbf1b005d8d6
出典データセット
uspto-grants-2009_09
特許番号
US07585975B2

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