Acetic Acid → N-[5-(6-chloro-3-cyano-1-methyl-1H-indol-2-yl)-pyridin-3-ylmethyl]-methanesulfonamide

HRID 593622Notes

Reaction equation

HRID 593622 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.[CH3:22][S:23]([NH2:26])(=[O:25])=[O:24].C(O)(=O)C.C(N(CC)CC)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:20]#[N:21])=[C:7]([C:12]3[CH:17]=[C:16]([CH2:18][NH:26][S:23]([CH3:22])(=[O:25])=[O:24])[CH:15]=[N:14][CH:13]=3)[N:8]2[CH3:11])=[CH:4][CH:3]=1

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 8471TriethylamineHCID 72879MethanesulfonamideHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 582157716-chloro-2-(5-formyl-pyridin-3-yl)-1-methyl-1H-indole-3-carbonitrile

Product 1

HCID 58215820N-[5-(6-chloro-3-cyano-1-methyl-1H-indol-2-yl)-pyridin-3-ylmethyl]-methanesulfonamide

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

6-Chloro-2-(5-formyl-pyridin-3-yl)-1-methyl-1H-indole-3-carbonitrile (Example 126, 50 mg, 0.169 mmol) and methanesulfonamide (24 mg, 0.254 mmol), acetic acid (20 mg, 0.338 mmol), triethylamine (34 mg, 0.338 mmol) in DCE (10 mL) are stirred for 30 min at ambient temperature before adding NaBH(OAc)3 (100 mg, 0.473 mmol). The reaction mixture is stirred overnight. NaHCO3 (1 mL) is added and the solvents are removed in vacuo. The residue is purified using a Sunfire C18 with a gradient of acetonitrile in 0.1% aqueous TFA and further purified with an Xbridge C18 using a gradient of acetonitrile in 0.1% NH4OH to give N-[5-(6-chloro-3-cyano-1-methyl-1H-indol-2-yl)-pyridin-3-ylmethyl]-methanesulfonamide as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.97 (s, 3H), 3.78 (s, 3H), 4.36 (s, 2H), 7.37 (dd, J=8.6, 1.8 Hz, 1H), 7.73 (d, J=8.6 Hz, 1H), 7.75 (br. s., 1H), 7.97 (d, J=1.8 Hz, 1H), 8.10 (t, J=2.1 Hz, 1H), 8.78 (d, J=2.0 Hz, 1H), 8.81 (d, J=2.3 Hz, 1H). HRMS (ESI) m/z 375.0681 [(M+H)+ Calcd for C17H16ClN4O2S: 375.0682].

Workup

  1. customthe solvents are removed in vacuo
  2. customThe residue is purified
  3. customfurther purified with an Xbridge

Sources & evidence

ORD record
ord-0e82c7c5b64e4ed7af6716c46fac7818
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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