Triethylamine → N4-[3-chloro-4-(3-fluoro-benzyloxy)-phenyl]-N6-(1-methyl-pyrrolidin-2-ylidene)-quinazoline-4,6-diamine

HRID 503717

反応式

HRID 503717 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.[CH3:29][N:30]1[CH2:34][CH2:33][CH2:32][C:31]1=O.P(Cl)(Cl)(Cl)=O.CCN(CC)CC>C(Cl)Cl>[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:31]4[CH2:32][CH2:33][CH2:34][N:30]4[CH3:29])[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

6

反応物 4

HCID 8471TriethylamineHCID 13387N-methyl-2-pyrrolidone2 回HCID 24813Phosphorus oxychlorideHCID 53630477Allitinib metabolite M62 回

生成物 1

HCID 57590588N4-[3-chloro-4-(3-fluoro-benzyloxy)-phenyl]-N6-(1-methyl-pyrrolidin-2-ylidene)-quinazoline-4,6-diamine収率 8%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

N4-[3-Chloro-4-(3-fluoro-benzyloxy)-phenyl]-N6-(1-methyl-pyrrolidin-2-ylidene)-quinazoline-4,6-diamine is prepared by reacting N4-[3-Chloro-4-(3-fluoro-benzyloxy)-phenyl]-quinazoline-4,6-diamine and 1-methyl-pyrrolidin-2-one. Phosphorous oxychloride (0.047 g, 0.30 mmol) is added to a stirred solution of 1-methyl-pyrrolidin-2-one (0.63 g, 0.63 mmol) in methylene chloride (3 ml) at −78° C. under N2 (Bullock et al WO0220526). After 10 minutes, the reaction mixture is warmed to room temperature and stirred for 1 hour. N4-[3-Chloro-4-(3-fluoro-benzyloxy)-phenyl]-quinazoline-4,6-diamine (0.100 g, 0.253 mmol) is added followed by Et3N (0.031 g, 0.30 mmol). After 16 hours, the reaction mixture is quenched with saturated aqueous Na2CO3, the layers separated and the aqueous layer extracted with methylene chloride. The combined organic extracts are dried (Na2SO4), concentrated and purified on a silica gel column (10:2:1 EtOAc:hexanes:MeOH with 0.3% NH4OH solution) to yield 0.010 g (8%) N4-[3-chloro-4-(3-fluoro-benzyloxy)-phenyl]-N6-(1-methyl-pyrrolidin-2-ylidene)-quinazoline-4,6-diamine. MS APCI (+) m/z 476, 478 (M+1, Cl pattern) detected; 1H NMR (400 MHz, MeOH d) δ 8.42 (s, 1H), 7.89 (s, 2H), 7.77 (d, 1H), 7.58 (m, 2H), 7.33 (m, 3H), 7.18 (d, 1H), 7.04 (t, 1H), 5.20 (s, 2H), 3.60 (t, 2H), 2.61 (t, 2H), 2.03 (m, 2H).

後処理

  1. customN4-[3-Chloro-4-(3-fluoro-benzyloxy)-phenyl]-N6-(1-methyl-pyrrolidin-2-ylidene)-quinazoline-4,6-diamine is prepared
  2. waitAfter 16 hours
  3. customthe reaction mixture is quenched with saturated aqueous Na2CO3
  4. customthe layers separated
  5. extractionthe aqueous layer extracted with methylene chloride
  6. dry with materialThe combined organic extracts are dried (Na2SO4)
  7. concentrationconcentrated
  8. custompurified on a silica gel column (10:2:1 EtOAc:hexanes:MeOH with 0.3% NH4OH solution)

出典と根拠

ORDレコード
ord-717f787b9a4a423188ee537cc8d811bc
出典データセット
uspto-grants-2010_08
特許番号
US07777032B2

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