Benzaldehyde → HCID 59534644, compound

HRID 1630908Notes

Reaction equation

HRID 1630908 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:20]#[N:21])=[C:7]([C:12]3[CH:13]=[N:14][CH:15]=[C:16]([CH:18]=O)[CH:17]=3)[N:8]2[CH3:11])=[CH:4][CH:3]=1.[NH2:22][CH:23]1[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]1.[BH3-]C#N.[Na+].C(=O)C1C=CC=CC=1>C1COCC1.CN(C=O)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:20]#[N:21])=[C:7]([C:12]3[CH:13]=[N:14][CH:15]=[C:16]([CH2:18][NH:22][CH:23]4[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]4)[CH:17]=3)[N:8]2[CH3:11])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 240BenzaldehydeHCID 27375314-Amino-1-methylpiperidineHCID 5003444Sodium cyanoborohydride2×HCID 582157716-chloro-2-(5-formyl-pyridin-3-yl)-1-methyl-1H-indole-3-carbonitrile

Product 1

HCID 59534644HCID 59534644, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-chloro-2-(5-formyl-pyridin-3-yl)-1-methyl-1H-indole-3-carbonitrile (Example 126, 0.150 g, 0.482 mmol) in THF (3 mL) and DMF (1 mL) is added 4-amino-1-methylpiperidine (0.067 g, 0.578 mmol), followed with MP—NaBH3CN (2.42 mmol/g, 0.498 g, 1.205 mmol). After 16 h, MP—NaBH3CN (2.42 mmol/g, 0.200 g, 0.484 mmol) is added. After another 46 h and PL-benzaldehyde (1.8 mmol/g, 0.268 g, 0.482 mmol) is added and after another 8 h, the mixture is filtered and the solids are washed with THF. After evaporation of the solvents, the residue is purified by reverse phase HPLC on a Sunfire C18, eluting with a gradient of 0.1% aqueous TFA-acetonitrile to give 6-chloro-1-methyl-2-{5-[(1-methyl-piperidin-4-ylamino)-methyl]-pyridin-3-yl}-1H-indole-3-carbonitrile as a gum which is triturated with 1M HCl in ether to give the HCl salt. 1H NMR (400 MHz, DMSO-d6) δ ppm (HCl salt) 1.46-1.66 (m, 2H), 1.93-2.04 (m, 2H), 2.50-2.57 (m, 4H), 2.66-2.76 (m, 2H), 3.10-3.20 (m, 2H), 3.80 (s, 3H), 3.95 (br. s., 2H), 7.37 (dd, J=8.6, 1.8 Hz, 1H), 7.73 (d, J=8.6 Hz, 1H), 7.98 (d, J=1.8 Hz, 1H), 8.16 (s, 1H), 8.79 (d, J=2.0 Hz, 1H), 8.80 (d, J=2.0 Hz, 1H). HRMS (ESI) m/z 394.1804 [(M+H)+ Calcd for C22H25ClN5: 394.1798].

Workup

  1. waitAfter another 46 h
  2. filtrationthe mixture is filtered
  3. washthe solids are washed with THF
  4. customAfter evaporation of the solvents
  5. customthe residue is purified by reverse phase HPLC on a Sunfire C18
  6. washeluting with a gradient of 0.1% aqueous TFA-acetonitrile

Sources & evidence

ORD record
ord-40ec52730ede4c03855acf97b623d7f0
Source dataset
uspto-grants-2014_07
Patent number
US08791141B2

Reaction notes

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