Pyridine → HCID 22676787, compound

HRID 1006270Notes

Reaction equation

HRID 1006270 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)(Cl)=[O:8].[NH2:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[N:17]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=1)[C:16]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[C:15]2[C:35]1[CH:40]=[CH:39][C:38]([C:41]([CH3:44])([CH3:43])[CH3:42])=[CH:37][CH:36]=1.C1(CN)CC1>ClCCl>[C:41]([C:38]1[CH:37]=[CH:36][C:35]([C:15]2[C:14]3[C:18](=[CH:19][CH:20]=[C:12]([NH:11][C:6]([NH:1][CH2:2][CH:3]4[CH2:5][CH2:4]4)=[O:8])[CH:13]=3)[N:17]([CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=3)[C:16]=2[C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:40][CH:39]=1)([CH3:43])([CH3:42])[CH3:44]

Participants

6

Reactant 4

HCID 1049PyridineHCID 6371PhosgeneHCID 75646CyclopropanemethanamineHCID 22676732HCID 22676732, compound

Product 1

HCID 22676787HCID 22676787, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

Pyridine (0.18 mL, 174 mg, 2.2 mmol) and phosgene (1.9 M in toluene, 0.66 mL, 1.2 mmol) were added to a cooled (0° C.) and stirred solution of ethyl 5-amino-3-(4-tert-butylphenyl)-1-(3-methoxybenzyl)-1H-indole-2-carboxylate (Example 160, 500 mg, 1.1 mmol) in dichloromethane (10 mL). The reaction was warmed to rt and stirred for 3 h. The solution was concentrated in vacuo leaving crude Example 172. A portion (260 mg, 0.54 mmol) of the intermediate was dissolved in dichloromethane (10 mL) and then (cyclopropylmethyl)amine (0.13 mL, 108 mg, 1.5 mmol) was added. The reaction was stirred at rt for 16 h and then diluted with dichloromethane (100 mL). The solution was washed with water and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. Flash chromatography of the residue over silica gel using 3:1 hexane/ethyl acetate gave 160 mg (54%) of the desired product. The product had: 1H NMR (300 MHz, acetone-D6) δ 8.08 (d, 1 H), 7.09-7.45 (m, 7 H), 6.60-6.78 (m, 3 H), 6.33 (dd, 1 H), 5.76 (s, 2 H), 3.91 (q, 2 H), 3.68 (s, 3 H), 1.32 (s, 3 H), 0.87-0.96 (m, 1 H), 0.72 (t, 3 H), 0.31-0.41 (m, 2 H), 0.11-0.21 (m, 2 H).

Workup

  1. temperatureThe reaction was warmed to rt
  2. concentrationThe solution was concentrated in vacuo
  3. customleaving crude Example 172
  4. stirringThe reaction was stirred at rt for 16 h
  5. washThe solution was washed with water and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b13cdd27aabb4fc7a6eacad7b398a493
Source dataset
uspto-grants-2004_09
Patent number
US06787651B2

Reaction notes

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