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 500448노트

반응식

HRID 500448 반응식
[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

참가 물질

5

반응물 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

생성물 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 salt수율 42.5%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-db3cb2b4656b403f9ff5bd255e5742a1
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07772227B2

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