1,2-Dichloroethane → HCID 22668223, compound

HRID 381771Notes

Reaction equation

HRID 381771 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[C:7]([C:19]1[C:20]([Cl:29])=[N:21][C:22]3[C:27]([CH:28]=1)=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:6]2.C1C=NC2N(O)N=NC=2C=1.C(N(CC)CC)C.C(Cl)CCl.[C:51]([N:58]1[CH2:63][CH2:62][CH:61]([C:64](O)=[O:65])[CH2:60][CH2:59]1)([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52]>CN(C=O)C>[C:54]([O:53][C:51]([N:58]1[CH2:63][CH2:62][CH:61]([C:64]([NH:1][CH2:2][C:3]2[CH:4]=[C:5]3[C:9](=[CH:10][CH:11]=2)[N:8]([C:12]([O:14][C:15]([CH3:17])([CH3:18])[CH3:16])=[O:13])[C:7]([C:19]2[C:20]([Cl:29])=[N:21][C:22]4[C:27]([CH:28]=2)=[CH:26][CH:25]=[CH:24][CH:23]=4)=[CH:6]3)=[O:65])[CH2:60][CH2:59]1)=[O:52])([CH3:57])([CH3:56])[CH3:55]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 181649HOAtHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 22668253HCID 22668253, compound

Product 1

HCID 22668223HCID 22668223, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of tert-butyl 5-(aminomethyl)-2-(2-chloro-3-quinolinyl)-1H-indole-1-carboxylate (7-4, 204 mg, 0.5 mmol, 1 equiv), HOAT (68 mg, 0.5 mmol, 1 equiv), triethylamine (101 mg, 1.0 mmol, 2 equiv), EDC (144 mg, 0.75 mmol, 1.5 equiv) and 1-BOC-piperidine-4-carboxylic acid (126 mg, 0.55 mmol, 1.1 equiv) in DMF (5 mL) was stirred under ambient conditions for 18 hr. The reaction was concentrated, and the residue was partitioned between ethyl acetate and saturated aqueous NaHCO3 solution. The organic layer was washed with brine, dried over magnesium sulfate and concentrated to provide tert-butyl 5-[({[1-(tert-butoxycarbonyl)-4-piperidinyl]carbonyl}amino)methyl]-2-(2-chloro-3-quinolinyl)-1H-indole-1-carboxylate (7-5) as a white foam. 1H NMR (400 MHz, CDCl3) δ8.25 (d, 1H, J=8 Hz), 8.16 (s, 1H), 8.05 (d, 1H, J=8 Hz), 7.85 (d, 1H, J=8 Hz), 7.76 (t, 1H, J=8 Hz), 7.59 (t, 1H, J=8 Hz), 7.49 (s, 1H), 7.28 (dd, 1H, J=8, 2 Hz), 6.61 (s, 1H), 4.48 (d, 2H, J=5 Hz), 4.12 (m, 2H), 2.72 (m, 2H), 2.26 (m, 1H), 1.84 (m, 2H), 1.65 (m, 2H), 1.42 (s, 9H), 1.25 (s, 9H).

Workup

  1. concentrationThe reaction was concentrated
  2. customthe residue was partitioned between ethyl acetate and saturated aqueous NaHCO3 solution
  3. washThe organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-914eaa4ec19d482ba04cb2d162f4a42a
Source dataset
uspto-grants-2001_10
Patent number
US06306874B1

Reaction notes

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