Diisopropylethylamine → (r)-3-Cyclohexyl-2,3-dihydro-6-[(cis)-4-benzyl-2,6-dimethylpiperazin-1-yl-carbonyl]pyrrolo[1,2,3-de]-1,4-benzoxazine hydrochloride salt

HRID 500448ノート

反応式

HRID 500448 の反応式
[CH:1]1([C@H:7]2[N:12]3[CH:13]=[C:14]([C:19]([Cl:21])=[O:20])[C:15]4[CH:16]=[CH:17][CH:18]=[C:10]([C:11]=43)[O:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.[CH2:31]([N:38]1[CH2:43][C@H:42]([CH3:44])[NH:41][C@H:40]([CH3:45])[CH2:39]1)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>ClCCl>[ClH:21].[CH:1]1([C@H:7]2[N:12]3[CH:13]=[C:14]([C:19]([N:41]4[C@H:42]([CH3:44])[CH2:43][N:38]([CH2:31][C:32]5[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=5)[CH2:39][C@@H:40]4[CH3:45])=[O:20])[C:15]4[CH:16]=[CH:17][CH:18]=[C:10]([C:11]=43)[O:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 12197174(3r,5s)-1-Benzyl-3,5-dimethylpiperazineHCID 87537363(R)-3-cyclohexyl-2,3-dihydropyrrolo[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid chloride

生成物 1

HCID 68674127(r)-3-Cyclohexyl-2,3-dihydro-6-[(cis)-4-benzyl-2,6-dimethylpiperazin-1-yl-carbonyl]pyrrolo[1,2,3-de]-1,4-benzoxazine hydrochloride salt収率 42.5%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of (R)-3-cyclohexyl-2,3-dihydropyrrolo[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid chloride (380 mg, 1.23 mmol) and N,N diisopropyl ethylamine (0.2 ml, 1.3 mmol) in dichloromethane (20 ml) was added 1-N-benzyl-(cis)3,5-dimethylpiperazine (250 mg, 1.2 mmol) in dichloromethane (5 ml) and the mixture was stirred for 16 h at room temperature. The mixture was partitioned between sodium bicarbonate solution and dichloromethane. The organic layer was separated and the solvent removed in vacuo. The residue was purified by flash chromatography eluting with 0-5% (v/v) methanol in dichloromethane. Hydrochloride salt formation was achieved by the addition of hydrogen chloride (2 M solution in diethyl ether; 2 ml) to the free base in dichloromethane (1 ml). The precipitate was filtered and dried to afford (R)-3-cyclohexyl-2,3-dihydro-6-[(cis)-4-benzyl-2,6-dimethylpiperazin-1-yl-carbonyl]pyrrolo[1,2,3-de]-1,4-benzoxazine hydrochloride salt as a light blue powder (240 mg, 0.51 mmol).

後処理

  1. customThe mixture was partitioned between sodium bicarbonate solution and dichloromethane
  2. customThe organic layer was separated
  3. customthe solvent removed in vacuo
  4. customThe residue was purified by flash chromatography
  5. washeluting with 0-5% (v/v) methanol in dichloromethane. Hydrochloride salt formation
  6. additionwas achieved by the addition of hydrogen chloride (2 M solution in diethyl ether; 2 ml) to the free base in dichloromethane (1 ml)
  7. filtrationThe precipitate was filtered
  8. customdried

出典と根拠

ORDレコード
ord-db3cb2b4656b403f9ff5bd255e5742a1
出典データセット
uspto-grants-2010_08
特許番号
US07772227B2

反応ノート

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