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

HRID 732281

반응식

HRID 732281 반응식
[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

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 13387N-methyl-2-pyrrolidone2회HCID 24813Phosphorus oxychlorideHCID 53630477Allitinib metabolite M62회

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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 d4) 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).

후처리

  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)

출처 및 근거

ORD 기록
ord-7bb762b439864e6780d967fd63241bbe
출처 데이터셋
uspto-grants-2009_09
특허 번호
US07585975B2

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