Bis(2-amino-1H-imidazole) sulphate → HCID 58026665, compound

HRID 1844957Notes

Reaction equation

HRID 1844957 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:11]([NH:13][C:14]2[NH:18][C:17]3[CH:19]=[CH:20][CH:21]=[C:22]([C:23]([OH:25])=O)[C:16]=3[N:15]=2)=[O:12])[N:2]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.S(O)(O)(=O)=O.[NH2:55][C:56]1[NH:57][CH:58]=[CH:59][N:60]=1>CN(C=O)C.CCN(C(C)C)C(C)C.[OH-].[Na+].[Cl-].[Na+].O>[NH:57]1[CH:58]=[CH:59][N:60]=[C:56]1[NH:55][C:23]([C:22]1[C:16]2[N:15]=[C:14]([NH:13][C:11]([C:3]3[N:2]=[CH:1][C:10]4[C:5]([CH:4]=3)=[CH:6][CH:7]=[CH:8][CH:9]=4)=[O:12])[NH:18][C:17]=2[CH:19]=[CH:20][CH:21]=1)=[O:25]

Participants

8

Reactant 3

HCID 135136Bis(2-amino-1H-imidazole) sulphateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66940354HCID 66940354, compound

Product 1

HCID 58026665HCID 58026665, compoundYield 21%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolvent2×HCID 14798Sodium HydroxideSolventHCID 81531DiisopropylethylamineSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

332 mg (1.0 mmol) of above 2-[(isoquinoline-3-carbonyl)-amino]-1H-benzoimidazole-4-carboxylic acid (0.33 g, 1.0 mmol) was reacted with 800 mg (2.0 mmol) of HBTU and 2-aminoimidazole sulfate (400 mg, 3.0 mmol) in 3.0 mL of DMF and 1.0 mL of DIEA as described in general procedure A. After cooling to room temperature, the reaction mixture was diluted with 0.6 mL of 5 N NaOH aq. solution and 4.0 mL of brine. The solid was collected by filtration and washed with 2 N NaOH aq. (3.0 mL), followed by H2O and EtOAc (3× of each), to give 224.0 mg of the crude compound. The crude was heated in 3.0 mL of DMF at 80° C. for 20 minutes. The filter cake was washed by another 1.0 mL of hot DMF. The combined filtrate was reheated to a clear solution, then cooled and addition of 2.0 mL of EtOAc, followed by 4.0 mL of H2O. The mixture was stirred, and a solid was gradually formed between EtOAc and DMF/H2O layers. The solid was collected by filtration and washed with H2O, EtOAc and MeOH (3× of each), then dried, to yield isoquinoline-3-carboxylic acid [4-(1H-imidazol-2-ylcarbamoyl)-1H-benzoimidazol-2-yl]-amide (83.0 mg, 21%). LCMS: 398.0 (M+1)+. 1H NMR (DMSO-d6, 400 MHz): δ 12.29 (s, 1H), 11.86 (s, 1H), 9.52 (s, 1H), 8.81 (s, 1H), 8.31 (t, 2H), 7.80-7.95 (m, 4H), 7.32 (t, 1H), 6.88 (s, 1H), 6.77 (s, 1H) ppm.

Workup

  1. filtrationThe solid was collected by filtration
  2. washwashed with 2 N NaOH aq. (3.0 mL)
  3. customto give 224.0 mg of the crude compound
  4. washThe filter cake was washed by another 1.0 mL of hot DMF
  5. temperaturecooled
  6. additionaddition of 2.0 mL of EtOAc
  7. customa solid was gradually formed between EtOAc and DMF/H2O layers
  8. filtrationThe solid was collected by filtration
  9. washwashed with H2O, EtOAc and MeOH (3× of each),
  10. customthen dried

Sources & evidence

ORD record
ord-5773c36cc57542b2a0548d45cd0fcd40
Source dataset
uspto-grants-2015_02
Patent number
US08946259B2

Reaction notes

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