Acetic Acid → HCID 9981880, 화합물

HRID 897027

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HRID 897027 반응식
[Cl:1][C:2]1[C:7]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([F:19])[CH:15]=3)[N:10]=[C:9]2[CH:20]=O)=[CH:6][CH:5]=[CH:4][N:3]=1.[N:22]1([CH2:27][C:28]2[CH:29]=[C:30]([CH:32]=[CH:33][CH:34]=2)[NH2:31])[CH2:26][CH2:25][CH2:24][CH2:23]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[Cl:1][C:2]1[C:7]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([F:19])[CH:15]=3)[N:10]=[C:9]2[CH2:20][NH:31][C:30]2[CH:32]=[CH:33][CH:34]=[C:28]([CH2:27][N:22]3[CH2:23][CH2:24][CH2:25][CH2:26]3)[CH:29]=2)=[CH:6][CH:5]=[CH:4][N:3]=1

참가 물질

6

반응물 4

HCID 176Acetic AcidHCID 10964073-(Pyrrolidin-1-ylmethyl)anilineHCID 5049666Sodium triacetoxyborohydrideHCID 12088007HCID 12088007, 화합물

생성물 1

HCID 9981880HCID 9981880, 화합물

시약·촉매·용매 1

HCID 63651,1-Dichloroethane용매

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온도
0 °C

실험 절차

A mixture of 3-(2-chloro-pyridin-3-yl)-6-fluoro-3,4-dihydro-quinazolin-4-one-2-carboxaldehyde (0.150 g, 0.49 mmol), 3-pyrrolidin-1-ylmethylaniline (0.044 g, 0.25 mmol), and acetic acid (0.14 mL, 2.45 mmol) in dichloroethane (10 mL) was chilled to 0° C. and sodium triacetoxyborohydride (0.312 g, 1.47 mmol) was added. The reaction was stirred for 1 hour at 0° C. and then allowed to warm to ambient temperature. The reaction was quenched by addition of saturated aqueous bicarbonate and continued stirring for 30 minutes. The phases were separated and the aqueous layer was extracted with methylene chloride. The combined organic phase was washed with brine, dried over magnesium sulfate and concentrated. The residue was flash chromatographed on silica gel (45 g) with elution proceeding as follows: 10% methanol/0.5% ammonium hydroxide/chloroform (200 mL), nil; (50 mL), unweighed impurity; (25 mL), nil; (75 mL), unweighed mixed fraction; (200 mL), 0.010 g (8%) of 3-(2-chloro-pyridin-3-yl)-6-fluoro-2-[(3-pyrrolidin-1-ylmethyl-phenylamino)-methyl]-3H-quinazolin-4-one as a pale yellow solid which had: 1H NMR δ 8.60 (d, J=5 Hz, 1 H), 7.80 (t, J=5 Hz, 1 H), 7.76 (d, J=9 Hz, 1 H), 7.71 (dd, J=3, 9 Hz, 1 H), 7.58-7.50 (m, 2 H), 7.35 (dd, J=5, 8 Hz, 1 H), 7.14-7.08 (m, 2 H), 6.80 (dd, J=4, 9 Hz, 1 H), 4.44 (s, 1 H), 3.90-3.65 (m, 4 H), 2.79 (br s, 4 H), 1.90 (br s, 4 H); APCI MS m/z=464 (P+1).

후처리

  1. temperatureto warm to ambient temperature
  2. customThe reaction was quenched by addition of saturated aqueous bicarbonate
  3. stirringcontinued stirring for 30 minutes
  4. customThe phases were separated
  5. extractionthe aqueous layer was extracted with methylene chloride
  6. washThe combined organic phase was washed with brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. customchromatographed on silica gel (45 g) with elution proceeding

출처 및 근거

ORD 기록
ord-1dca32f1e15d476dae110ebf69c516c0
출처 데이터셋
uspto-grants-2005_07
특허 번호
US06921764B2

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