Hydrochloric Acid → 1-[(4R)-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea

HRID 868888

반응식

HRID 868888 반응식
C1C(=O)N(OC(ON2C(=O)CCC2=O)=O)[C:3](=[O:4])C1.N1C=CC=CC=1.[NH2:25][C:26]1[CH:35]=[CH:34][CH:33]=[C:32]2[C:27]=1[CH2:28][NH:29][C:30](=[O:37])[N:31]2[CH3:36].C(N(CC)C(C)C)(C)C.O[C@H](C1C=CC=CC=1)C([O-])=O.[CH3:58][C:59]1([CH3:70])[CH2:68][C@@H:67]([NH2:69])[C:66]2[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=2)[O:60]1.Cl>CCOC(C)=O.C(#N)C>[CH3:58][C:59]1([CH3:70])[CH2:68][C@@H:67]([NH:69][C:3]([NH:25][C:26]2[CH:35]=[CH:34][CH:33]=[C:32]3[C:27]=2[CH2:28][NH:29][C:30](=[O:37])[N:31]3[CH3:36])=[O:4])[C:66]2[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=2)[O:60]1

참가 물질

10

반응물 7

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 81531DiisopropylethylamineHCID 676246Di(succinimido) carbonateHCID 5460269(R)-MandelateHCID 42157625(R)-2,2-dimethylchroman-4-amineHCID 574159275-amino-1-methyl-3,4-dihydroquinazolin-2(1H)-one

생성물 1

HCID 716114831-[(4R)-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea수율 88.2%

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

실험 절차

A slurry of N,N-disuccinimidyl carbonate (434 mg, 1.69 mmol), acetonitrile (6 mL), pyridine (0.137 mL, 1.69 mmol), and 5-amino-1-methyl-3,4-dihydroquinazolin-2(1H)-one (A-1) (300 mg, 1.69 mmol) was stirred at room temperature. After 45 min, N,N-diisopropylethylamine (0.879 mL, 5.08 mmol) and (R)-2-hydroxy-2-phenylacetate salt of (R)-2,2-dimethylchroman-4-amine (B-2) (558 mg, 1.69 mmol) were added. After 30 minutes, EtOAc (50 mL) and 2N aqueous HCl (20 mL) were added and the layers separated. The organic extract was washed with brine (10 mL), dried (Na2SO4), filtered, and concentrated. The residue was purified by silica gel chromatography (0-10% MeOH/EtOAc gradient) to afford the title compound (565 mg, 1.49 mmol, 88% yield). 1H NMR (300 MHz, DMSO-d6) δ 7.80 (s, 1H), 7.42 (d, J=8.1 Hz, 1H), 7.25 (t, J=10.7 Hz, 1H), 7.16 (dd, J=16.6, 8.2 Hz, 3H), 6.89 (t, J=7.0 Hz, 1H), 6.73 (d, J=8.6 Hz, 2H), 6.63 (d, J=8.1 Hz, 1H), 4.94 (dd, J=15.2, 10.0 Hz, 1H), 4.18 (s, 2H), 3.14 (s, 3H), 2.13 (dd, J=13.2, 6.2 Hz, 1H), 1.69 (dd, J=30.9, 18.0 Hz, 1H), 1.39 (s, 3H), 1.27 (s, 3H). MS (ESI+) m/z 449 (M+H)+.

후처리

  1. waitAfter 30 minutes
  2. customthe layers separated
  3. extractionThe organic extract
  4. washwas washed with brine (10 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (0-10% MeOH/EtOAc gradient)

출처 및 근거

ORD 기록
ord-c2f3ef860df64005a91eeb46460def2f
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08969325B2

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