1,2-Dichloroethane → Benzyl 9-(5-{[(2-aminophenyl)amino]carbonyl}pyridin-2-yl)-3,9-diazaspiro[5.5]-undecane-3-carboxylate

HRID 1802569

반응식

HRID 1802569 반응식
C[O:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]([N:11]2[CH2:28][CH2:27][C:14]3([CH2:19][CH2:18][N:17]([C:20]([O:22]C(C)(C)C)=[O:21])[CH2:16][CH2:15]3)[CH2:13][CH2:12]2)=[N:9][CH:10]=1)=O.CCN(CC)CC.C(Cl)(O[CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)=O.O[Li].O.C(Cl)CCl.[CH:54]1[CH:55]=[CH:56][C:57]2[N:62](O)N=[N:60][C:58]=2[CH:59]=1.C1(N)C=CC=CC=1N>C(Cl)Cl.C(O)(C(F)(F)F)=O.CO.C1COCC1.O>[NH2:60][C:58]1[CH:59]=[CH:54][CH:55]=[CH:56][C:57]=1[NH:62][C:3]([C:5]1[CH:6]=[CH:7][C:8]([N:11]2[CH2:28][CH2:27][C:14]3([CH2:19][CH2:18][N:17]([C:20]([O:22][CH2:39][C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)=[O:21])[CH2:16][CH2:15]3)[CH2:13][CH2:12]2)=[N:9][CH:10]=1)=[O:2]

참가 물질

11

반응물 7

HCID 111,2-DichloroethaneHCID 7243O-PhenylenediamineHCID 8471TriethylamineHCID 10387Benzyl chloroformateHCID 757711-HydroxybenzotriazoleHCID 168937Lithium hydroxide, monohydrateHCID 57717452Tert-butyl 9-[5-(methoxycarbonyl)pyridin-2-yl]-3,9-diazaspiro[5.5]undecane-3-carboxylate

생성물 1

HCID 57717481Benzyl 9-(5-{[(2-aminophenyl)amino]carbonyl}pyridin-2-yl)-3,9-diazaspiro[5.5]-undecane-3-carboxylate

시약·촉매·용매 3

HCID 6344Dichloromethane용매HCID 6422Trifluoroacetic acid용매HCID 21892291Methanol tetrahydrofuran water용매

실험 절차

A solution of tert-butyl 9-[5-(methoxycarbonyl)pyridin-2-yl]-3,9-diazaspiro[5.5]undecane-3-carboxylate (100 mg, 0.257 mmol) in 1 mL of CH2Cl2 and 1 mL of TFA was stirred for 1 h and concentrated. The oil was redissolved in 2 mL of CH2Cl2 and treated with NEt3 (0.15 mL, 1.08 mmol) and CbzCl (0.060 mL, 0.42 mmol), then stirred for 8 h. The mixture was partitioned between EtOAc and sat'd NaHCO3, dried (Na2SO4), filtered and concentrated. The residue was stirred in 3 mL of 1:1:1 MeOH/THF/water with LiOH.H2O (30 mg, 0.71 mmol) for 10 h, concentrated to dryness, dissolved in 2 mL of DMF, treated with EDC (150 mg, 0.79 mmol), HOBt (100 mg, 0.74 mmol), and phenylenediamine (100 mg, 0.93 mmol). The mixture was stirred for 18 h, concentrated, and triturated with methanol giving the title compound; MS (ESI+): cal'd [M+1]+ 500.3, obs'd 500.3.

후처리

  1. concentrationconcentrated
  2. dissolutionThe oil was redissolved in 2 mL of CH2Cl2
  3. customThe mixture was partitioned between EtOAc
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. concentrationconcentrated to dryness
  8. dissolutiondissolved in 2 mL of DMF
  9. stirringThe mixture was stirred for 18 h
  10. concentrationconcentrated
  11. customtriturated with methanol giving the title compound

출처 및 근거

ORD 기록
ord-2d9448d38eed4dd5b9d6b048baa9b3cf
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08349825B2

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