Formaldehyde → 3-(1-cyano-1-methylethyl)-N-[3-({2-[(cyclopropylcarbonyl)amino]-7-(dimethylamino)-1,3-benzothiazol-6-yl}oxy)phenyl]benzamide

HRID 455230Notes

Reaction equation

HRID 455230 reaction equation
N[C:2]1[C:10]2[S:9][C:8]([NH:11][C:12]([CH:14]3[CH2:16][CH2:15]3)=[O:13])=[N:7][C:6]=2[CH:5]=[CH:4][C:3]=1[O:17][C:18]1[CH:19]=[C:20]([NH:24][C:25](=[O:37])[C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([C:35]#[N:36])([CH3:34])[CH3:33])[CH:27]=2)[CH:21]=[CH:22][CH:23]=1.[CH2:38]=O.[C:40]([BH3-])#[N:41].[Na+]>C(O)(=O)C.C(OCC)(=O)C>[C:35]([C:32]([C:28]1[CH:27]=[C:26]([CH:31]=[CH:30][CH:29]=1)[C:25]([NH:24][C:20]1[CH:21]=[CH:22][CH:23]=[C:18]([O:17][C:3]2[CH:4]=[CH:5][C:6]3[N:7]=[C:8]([NH:11][C:12]([CH:14]4[CH2:16][CH2:15]4)=[O:13])[S:9][C:10]=3[C:2]=2[N:41]([CH3:40])[CH3:38])[CH:19]=1)=[O:37])([CH3:34])[CH3:33])#[N:36]

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 59454488N-[3-({7-amino-2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazol-6-yl}oxy)phenyl]-3-(1-cyano-1-methylethyl)benzamide

Product 1

HCID 594545003-(1-cyano-1-methylethyl)-N-[3-({2-[(cyclopropylcarbonyl)amino]-7-(dimethylamino)-1,3-benzothiazol-6-yl}oxy)phenyl]benzamideYield 68.4%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-[3-({7-amino-2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazol-6-yl}oxy)phenyl]-3-(1-cyano-1-methylethyl)benzamide (100 mg, 0.195 mmol) produced in Example 43 in acetic acid (2 mL) were added para-formaldehyde (36 mg, 1.19 mmol) and sodium cyanoborohydride (45 mg, 0.644 mmol), and the mixture was stirred at room temperature for 12 hr. The reaction mixture was diluted with ethyl acetate (10 mL), washed successively with saturated aqueous sodium hydrogen carbonate solution (10 mL) and saturated brine (10 mL), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (ethyl acetate/n-hexane=20/80→80/20), and the obtained solution was concentrated under reduced pressure. The residue was crystallized from ethyl acetate/n-hexane to give the title compound (72 mg, 68%) as a white powder.

Workup

  1. washwashed successively with saturated aqueous sodium hydrogen carbonate solution (10 mL) and saturated brine (10 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationInsoluble material was filtered off
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe obtained residue was purified by basic silica gel column chromatography (ethyl acetate/n-hexane=20/80→80/20)
  6. concentrationthe obtained solution was concentrated under reduced pressure
  7. customThe residue was crystallized from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-8e7b53ac67a24a5a844f7f5fd3bc54ac
Source dataset
uspto-grants-2013_07
Patent number
US08497274B2

Reaction notes

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