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Diisopropylethylamine → (+/-)-4-[(3,3-Dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoic acid ethyl ester

HRID 2281127
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HRID 2281127 반응식
[CH2:1]([O:3][C:4](=[O:19])[C:5]1[CH:10]=[CH:9][C:8]([CH:11]([NH2:18])[CH:12]2[CH2:15][C:14]([CH3:17])([CH3:16])[CH2:13]2)=[CH:7][CH:6]=1)[CH3:2].[CH3:20][C:21]1[CH:22]=[N+:23]([O-])[C:24]2[C:29]([CH:30]=1)=[CH:28][CH:27]=[CH:26][CH:25]=2.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1>ClCCl>[CH2:1]([O:3][C:4](=[O:19])[C:5]1[CH:10]=[CH:9][C:8]([CH:11]([CH:12]2[CH2:13][C:14]([CH3:16])([CH3:17])[CH2:15]2)[NH:18][C:22]2[C:21]([CH3:20])=[CH:30][C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:23]=2)=[CH:7][CH:6]=1)[CH3:2]
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참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 70214663-Methylquinoline N-oxideHCID 71243808(+/-)-4-[Amino-(3,3-dimethyl-cyclobutyl)-methyl]-benzoic acid ethyl ester2회

생성물 1

HCID 71243836(+/-)-4-[(3,3-Dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoic acid ethyl ester수율 64.3%

시약·촉매·용매

1
HCID 6344Dichloromethane용매

실험 절차

(+/−)-4-[amino-(3,3-dimethyl-cyclobutyl)-methyl]-benzoic acid ethyl ester (Intermediate 24) (45 mg, 0.17 mmol) was combined with 3-methylquinoline-N-oxide (27.4 mg, 0.172 mmol, Alfa Aesar, Ward Hill, Mass., USA) and dichloromethane (2 mL). Diisopropylethylamine (0.112 mL, 0.645 mmol) was added followed by bromotripyrrolidinophosphonium hexafluorophosphate (109 mg, 0.224 mmol). The solution was stirred at room temperature for 28 h before partitioning between ethyl acetate and aq. sat. NaHCO3. The separated aqueous layer was extracted with additional ethyl acetate and the combined organics dried over MgSO4. Purification by silica gel flash chromatography (ethyl acetate/heptane) gave (+/−)-4-[(3,3-dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoic acid ethyl ester (44.0 mg) as a clear oil. 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J=8.4 Hz, 2 H) 7.56-7.62 (m, 2 H) 7.46-7.53 (m, 3 H) 7.38-7.46 (m, 1 H) 7.12-7.20 (m, 1 H) 5.33 (dd, J=9.5, 6.7 Hz, 1 H) 4.77 (d, J=6.6 Hz, 1 H) 4.34 (q, J=7.2 Hz, 2 H) 2.67 (sxt, J=8.8 Hz, 1 H) 2.30 (s, 3 H) 1.97 (ddd, J=11.1, 8.1, 3.2 Hz, 1 H) 1.74-1.85 (m, 1 H) 1.66-1.73 (m, 2 H) 1.36 (t, J=7.1 Hz, 3 H) 1.16 (s, 3 H) 1.10 (s, 3 H); MS (M+1): 403.3.

후처리

  1. custombefore partitioning between ethyl acetate and aq. sat. NaHCO3
  2. extractionThe separated aqueous layer was extracted with additional ethyl acetate
  3. dry with materialthe combined organics dried over MgSO4
  4. customPurification by silica gel flash chromatography (ethyl acetate/heptane)

출처 및 근거

ORD 기록
ord-7d768e7b97504ca693c6b8a806862d44
출처 데이터셋
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09139538B2

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