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

HRID 1802569

Reaction equation

HRID 1802569 reaction equation
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]

Participants

11

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolventHCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-2d9448d38eed4dd5b9d6b048baa9b3cf
Source dataset
uspto-grants-2013_01
Patent number
US08349825B2

Linked notes

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