4-(Methylsulfonyl)benzyl Bromide → (R)-2-chloro-5-(4-(methylsulfonyl)benzyl)-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine

HRID 2169545ノート

反応式

HRID 2169545 の反応式
[CH3:1][S:2]([C:5]1[CH:12]=[CH:11][C:8]([CH2:9]Br)=[CH:7][CH:6]=1)(=[O:4])=[O:3].[Cl:13][C:14]1[N:23]=[CH:22][C:21]2[NH:20][CH2:19][C@@H:18]3[CH2:24][O:25][CH2:26][CH2:27][N:17]3[C:16]=2[N:15]=1.CC(C)([O-])C.[K+]>CS(C)=O.CCOC(C)=O.O>[Cl:13][C:14]1[N:23]=[CH:22][C:21]2[N:20]([CH2:9][C:8]3[CH:11]=[CH:12][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:6][CH:7]=3)[CH2:19][C@@H:18]3[CH2:24][O:25][CH2:26][CH2:27][N:17]3[C:16]=2[N:15]=1

参加物

7

反応物 3

HCID 27335814-(Methylsulfonyl)benzyl BromideHCID 23665647Potassium tert-butoxideHCID 86670088(R)-2-chloro-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine

生成物 1

HCID 86670093(R)-2-chloro-5-(4-(methylsulfonyl)benzyl)-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine収率 32.1%

試薬・触媒・溶媒 3

HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

実験手順

4-Methylsulphonylbenzyl bromide (121 mg, 0.485 mmol) was added to a mixture of (R)-2-chloro-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine (PREPARATION x3, 100 mg, 0.441 mmol) and potassium tert-butoxide (59.4 mg, 0.529 mmol) in DMSO (2206 μL) at room temperature. The resultant mixture was stirred overnight at room temperature and subsequently diluted with EtOAc and water. The mixture was extracted twice with EtOAc. The combined extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO2, eluting with 0-10% MeOH/CHCl3 gradient) to afford the title compound as an off-white solid (55.9 mg, 32%). 1H NMR (400 MHz, DMSO-d6) δ 2.94-3.06 (m, 1 H), 3.08-3.29 (m, 5 H), 3.35-3.52 (m, 2 H), 3.67-3.76 (m, 1 H), 3.86-4.01 (m, 2 H), 4.25 (dd, J=13.64, 1.77 Hz, 1 H), 4.55 (s, 2 H), 7.30 (s, 1 H), 7.57 (d, J=8.34 Hz, 2 H), 7.87-7.92 (m, 2 H). ESI-MS m/z [M+H]+ calc'd for C17H19ClN4O3S, 395.09; found 395.2.

後処理

  1. extractionThe mixture was extracted twice with EtOAc
  2. washThe combined extracts were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (SiO2, eluting with 0-10% MeOH/CHCl3 gradient)

出典と根拠

ORDレコード
ord-ea484703e99149ab8edab3be406fc2c7
出典データセット
uspto-grants-2015_06
特許番号
US09045496B2

反応ノート

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