Acetic Acid → HCID 68684137, compound

HRID 2234311Notes

Reaction equation

HRID 2234311 reaction equation
[Cl:1][C:2]1[C:3]([NH:17][C:18]2[N:28]=[C:27]3[C:21]([N:22]([CH3:35])[C:23](=[O:34])[CH2:24][CH2:25][N:26]3[CH:29]3[CH2:33][CH2:32][CH2:31][CH2:30]3)=[CH:20][N:19]=2)=[CH:4][C:5]([F:16])=[C:6]([CH:15]=1)[C:7]([NH:9][C@@H:10]1[CH2:14][CH2:13][NH:12][CH2:11]1)=[O:8].[C:36](O)(=O)C.C([O-])(=O)C.[Na+].C([BH3-])#N.[Na+]>C=O>[Cl:1][C:2]1[C:3]([NH:17][C:18]2[N:28]=[C:27]3[C:21]([N:22]([CH3:35])[C:23](=[O:34])[CH2:24][CH2:25][N:26]3[CH:29]3[CH2:33][CH2:32][CH2:31][CH2:30]3)=[CH:20][N:19]=2)=[CH:4][C:5]([F:16])=[C:6]([CH:15]=1)[C:7]([NH:9][C@@H:10]1[CH2:14][CH2:13][N:12]([CH3:36])[CH2:11]1)=[O:8]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 517045Sodium AcetateHCID 5003444Sodium cyanoborohydrideHCID 68683529HCID 68683529, compound

Product 1

HCID 68684137HCID 68684137, compoundYield 70.4%

Reagents, catalysts & solvents 1

HCID 712FormaldehydeSolvent

Procedure

5-chloro-4-[(2-cyclopentyl-6-methyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-2-fluoro-N-[(3R)-pyrrolidin-3-yl]benzamide (Example 321; 95 mg, 0.19 mmol) was dissolved in 37% aqueous formaldehyde solution (1.1 mL) and acetic acid (120 μl, 1.89 mmol). Sodium acetate (156 mg, 1.89 mmol) was added and the mixture cooled in an ice/water bath. Sodium cyanoborohydride (12 mg, 0.19 mmol) was added and the mixture allowed to warm to room temperature. After stirring for 1 hour, the mixture was absorbed on to an SCX column, and subsequently washed with methanol and eluted with ammonia in methanol. The product containing fractions were concentrated and purified by column chromatography (2% 7N ammonia in methanol/DCM) to yield the title compound as a white foam (69 mg, 70%).

Workup

  1. temperaturethe mixture cooled in an ice/water bath
  2. customthe mixture was absorbed on to an SCX column
  3. washsubsequently washed with methanol
  4. washeluted with ammonia in methanol
  5. additionThe product containing fractions
  6. concentrationwere concentrated
  7. custompurified by column chromatography (2% 7N ammonia in methanol/DCM)

Sources & evidence

ORD record
ord-303cb4fd17304140ba071a4c62a3a8c9
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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