Dimethylformamide → HCID 59341078, compound

HRID 14695Notes

Reaction equation

HRID 14695 reaction equation
C(Cl)(=O)C(Cl)=O.O=C1C2C(=CC=CC=2)C(=O)[N:9]1[CH2:18][C:19]1[C:28]2[C:23](=[CH:24][C:25]([O:31][CH3:32])=[CH:26][C:27]=2[O:29][CH3:30])[C:22]([NH:33][C:34]2[S:35][CH:36]=[C:37](C(O)=O)[N:38]=2)=[CH:21][N:20]=1.[CH3:42][N:43]([CH:45]=[O:46])C.CN>ClCCl>[CH3:42][NH:43][C:45]([C:37]1[N:38]=[C:34]([NH:33][C:22]2[C:23]3[C:28](=[C:27]([O:29][CH3:30])[CH:26]=[C:25]([O:31][CH3:32])[CH:24]=3)[C:19]([CH2:18][NH2:9])=[N:20][CH:21]=2)[S:35][CH:36]=1)=[O:46]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 6329MethylamineHCID 65578Oxalyl chlorideHCID 593410932-[1-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-6,8-dimethoxy-isoquinolin-4-ylamino]-thiazole-4-carboxylic acid

Product 1

HCID 59341078HCID 59341078, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (8 μL, 0.092 mmol) was added to a solution of Example 49A (30 mg, 0.061 mmol) in dichloromethane (4 mL). Catalytic DMF was added, and the reaction stirred for 1 h. Methylamine (180 μL, 2M in THF, 0.366 mmol) was added, and the reaction stirred for 30 min. Organics were washed with brine, dried (MgSO4) and concentrated. Deprotection was carried out with hydrazine (0.2 mL) in methanol (3 mL), stirring for 1 h. Purification by Prep-HPLC gave 17.8 mg (60%) of the title compound (TFA salt) as a yellow solid. H1-NMR (MeOD-d4): δ 9.16 (s, 1H), 7.51 (s, 1H), 7.18 (s, 1H), 6.86 (s, 1H), 4.83 (s, 2H), 4.05 (s, 3H), 3.98 (s, 3H), 2.91 (s, 3H). MS (ES) (M+H) calc'd for C17H19N5O3S, 374; found 374.

Workup

  1. stirringthe reaction stirred for 30 min
  2. washOrganics were washed with brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. stirringstirring for 1 h
  6. customPurification by Prep-HPLC

Sources & evidence

ORD record
ord-6c6439f2123f4aecacb7b07cb0d4b844
Source dataset
uspto-grants-2010_06
Patent number
US07732446B1

Reaction notes

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