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

反応式

HRID 868888 の反応式
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

参加物

10

反応物 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

生成物 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)urea収率 88.2%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-c2f3ef860df64005a91eeb46460def2f
出典データセット
uspto-grants-2015_03
特許番号
US08969325B2

関連ノート

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