Acetic Acid → HCID 68467418, compound

HRID 506176Notes

Reaction equation

HRID 506176 reaction equation
[CH:1]([C:3]1[CH:4]=[CH:5][C:6]2[S:10][C:9]([C:11]3[CH:12]=[N:13][CH:14]=[C:15]([C:18]=3[NH:19][C:20]3[CH:28]=[CH:27][CH:26]=[C:25]4[C:21]=3[CH:22]=[CH:23][NH:24]4)[C:16]#[N:17])=[CH:8][C:7]=2[CH:29]=1)=O.[CH3:30][NH:31][CH3:32].C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C1COCC1>[CH3:30][N:31]([CH2:1][C:3]1[CH:4]=[CH:5][C:6]2[S:10][C:9]([C:11]3[CH:12]=[N:13][CH:14]=[C:15]([C:18]=3[NH:19][C:20]3[CH:28]=[CH:27][CH:26]=[C:25]4[C:21]=3[CH:22]=[CH:23][NH:24]4)[C:16]#[N:17])=[CH:8][C:7]=2[CH:29]=1)[CH3:32]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 674Dimethylamine2×HCID 5049666Sodium triacetoxyborohydrideHCID 86616831HCID 86616831, compound

Product 1

HCID 68467418HCID 68467418, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To 5-(5-formyl-1-benzothien-2-yl)-4-(1H-indol-4-ylamino)nicotinonitrile 223 (166 mg, 0.38 mmol) in THF (7 mL) was added dimethylamine in THF (2.0 M, 0.58 mL, 1.15 mmol) followed by acetic acid (126 mg, 2.09 mmol). The resulting mixture was stirred at r.t. for 1 h and additional dimethylamine (1.2 mL, 2.30 mmol) was added. After stirring at r.t. for an additional hour, Na(OAc)3BH (242 mg, 1.15 mmol) was added. The reaction mixture was stirred at r.t. for 2 h and was partitioned between diluted HCl and EtOAc. The combined aqueous extracts were basified with aqueous NaHCO3 and extracted with EtOAc. The combined organics were dried over Na2SO4, concentrated and purified by flash column chromatography to give 115 mg (65%) of 5-{5-[(dimethylamino)methyl]-1-benzothien-2-yl}-4-(1H-indol-4-ylamino)nicotinonitrile 224 as a pale yellow solid. MS: 424.2 (M+H); HPLC retention time: 2.1 min.(a).

Workup

  1. stirringAfter stirring at r.t. for an additional hour
  2. stirringThe reaction mixture was stirred at r.t. for 2 h
  3. customwas partitioned between diluted HCl and EtOAc
  4. extractionextracted with EtOAc
  5. dry with materialThe combined organics were dried over Na2SO4
  6. concentrationconcentrated
  7. custompurified by flash column chromatography

Sources & evidence

ORD record
ord-1f4f9017616b4df89f1f433e248de6fd
Source dataset
uspto-grants-2010_08
Patent number
US07781591B2

Reaction notes

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