Oxalyl chloride → HCID 10169295, compound

HRID 971377Notes

Reaction equation

HRID 971377 reaction equation
[CH:1]([O:4][C:5]1[N:10]=[C:9]([C:11](O)=[O:12])[CH:8]=[CH:7][C:6]=1[N+:14]([O-])=O)([CH3:3])[CH3:2].C(Cl)(C(Cl)=O)=O.[NH2:23][C:24]1[CH:25]=[CH:26][C:27]([C:34]([NH:36][C:37]2[CH:38]=[CH:39][C:40]([C:47]([NH:49][C:50]3[CH:51]=[CH:52][C:53]([C:60]([O:62][CH3:63])=[O:61])=[N:54][C:55]=3[O:56][CH:57]([CH3:59])[CH3:58])=[O:48])=[N:41][C:42]=2[O:43][CH:44]([CH3:46])[CH3:45])=[O:35])=[N:28][C:29]=1[O:30][CH:31]([CH3:33])[CH3:32].CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C>[NH2:14][C:6]1[CH:7]=[CH:8][C:9]([C:11]([NH:23][C:24]2[CH:25]=[CH:26][C:27]([C:34]([NH:36][C:37]3[CH:38]=[CH:39][C:40]([C:47]([NH:49][C:50]4[CH:51]=[CH:52][C:53]([C:60]([O:62][CH3:63])=[O:61])=[N:54][C:55]=4[O:56][CH:57]([CH3:59])[CH3:58])=[O:48])=[N:41][C:42]=3[O:43][CH:44]([CH3:46])[CH3:45])=[O:35])=[N:28][C:29]=2[O:30][CH:31]([CH3:32])[CH3:33])=[O:12])=[N:10][C:5]=1[O:4][CH:1]([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 10231511HCID 10231511, compoundHCID 10632978HCID 10632978, compound

Product 1

HCID 10169295HCID 10169295, compoundYield 93%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

6-Isopropoxy-5-nitro-2-pyridinecarboxylic acid (24.0 mg, 0.105 mmol), (COCl)2 (0.268 g, 2.12 mmol, 20 eqv), and DMF (cat.) were dissolved in 3 ml of CH2Cl2. The solution was allowed to stir for 2 h at rt and was then concentrated in vacuo. A solution of Methyl 5-{[(5-{[(5-amino-6-isopropoxy-2-pyridinyl)carbonyl]amino}-6-isopropoxy-2-pyridinyl)carbonyl]amino}-6-isopropoxy-2-pyridinecarboxylate (6-1b) (30.0 mg, 0.052 mmol, 0.5 eqv) and DIEA (27.3 mg, 0.21 mmol, 2.0 eqv) in 3 ml of CH2Cl2 was added to the crude acid chloride. The solution was stirred for 12 h at rt. The precipitate was filtered, and washed several times with cold CH2Cl2. The nitro-derivative and 10% Pd/C (5 mg) were added to 5 ml of 1:1 MeOH/CH2Cl2 and the suspension was stirred for 20 min at rt under 1 atm H2. The solution was filtered through celite and the filtrate was concentrated in vacuo to give 36 mg of a white solid (92%): 1H NMR (500 MHz, CDCl3) d 1.45 (d, J=6.5 Hz, 6H), 1.50 (d, J=6.5 Hz, 6H), 1.54 (d, J=6.0 Hz, 12H), 3.94 (s, 3H), 5.55 (m, 1H), 5.68 (m, 3H), 7.00 (d, J=7.5 Hz, 1H), 7.75 (d, J=8.0 Hz, 1H), 7.79 (d, J=8.0 Hz, 1H), 7.94 (d, J=8.0 Hz, 2H), 8.92 (d, J=8.0 Hz, 1H), 9.03 (dd, J1=8.0 Hz, J2=8.0 Hz 2H), 10.24 (s, 1H), 10.27 (s, 1H), 10.28 (s, 1H); 13C NMR (125 MHz, CDCl3) d 22.17, 22.17, 22.20, 22.20, 52.35, 68.56, 69.23, 69.33, 69.36, 117.32, 117.42, 117.86, 119.03, 120.02, 125.03, 125.83, 126.12, 126.63, 126.81, 127.25, 134.52, 135.33, 137.88, 138.71, 139.22, 149.67, 150.81, 150.87, 151.93, 162.78, 162.80, 163.46, 165.47; HRMS (FAB) Submitted.

Workup

  1. concentrationwas then concentrated in vacuo
  2. stirringThe solution was stirred for 12 h at rt
  3. filtrationThe precipitate was filtered
  4. washwashed several times with cold CH2Cl2
  5. additionThe nitro-derivative and 10% Pd/C (5 mg) were added to 5 ml of 1:1 MeOH/CH2Cl2
  6. stirringthe suspension was stirred for 20 min at rt under 1 atm H2
  7. filtrationThe solution was filtered through celite
  8. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-d0980ea2a2f34e8da96b908fdc3d6975
Source dataset
uspto-grants-2007_12
Patent number
US07312246B2

Reaction notes

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