Methanol → 2-Chloro-5-phenyl-6-[4-({[4-(1,2,3-thiadiazol-4-yl)benzyl]amino}methyl)phenyl]nicotinonitrile

HRID 2219075Notes

Reaction equation

HRID 2219075 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:15][C:12]([C:13]#[N:14])=[C:11]([Cl:23])[N:10]=2)=[CH:5][CH:4]=1.CO.[S:26]1[CH:30]=[C:29]([C:31]2[CH:36]=[CH:35][C:34]([CH2:37][NH2:38])=[CH:33][CH:32]=2)[N:28]=[N:27]1.CCN(C(C)C)C(C)C>C1COCC1>[Cl:23][C:11]1[N:10]=[C:9]([C:6]2[CH:7]=[CH:8][C:3]([CH2:2][NH:38][CH2:37][C:34]3[CH:33]=[CH:32][C:31]([C:29]4[N:28]=[N:27][S:26][CH:30]=4)=[CH:36][CH:35]=3)=[CH:4][CH:5]=2)[C:16]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:15][C:12]=1[C:13]#[N:14]

Participants

6

Reactant 4

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 27372881-[4-(1,2,3-Thiadiazol-4-Yl)phenyl]methanamineHCID 866076536-[4-(Bromomethyl)phenyl]-2-chloro-5-phenylnicotinonitrile

Product 1

HCID 111911212-Chloro-5-phenyl-6-[4-({[4-(1,2,3-thiadiazol-4-yl)benzyl]amino}methyl)phenyl]nicotinonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To the solution of 6-[4-(bromomethyl)phenyl]-2-chloro-5-phenylnicotinonitrile (2-5) 0.294 g, 0.766 mmol) in THF (5 mL) and MeOH (5 mL) was added 1-[4-(1,2,3-thiadiazol-4-yl)phenyl]methanamine (0.147 g, 0.766 mmol) and DIPEA (0.495 g, 3.831 mmol). The mixture wsa stirred overnight and concentrated. The residue was treated with aqueous Na2CO3 solution (2 M, 10 mL) and extracted with CH2Cl2 (3×30 mL). The combined organic layer was dried, filtered and concentrated. The residue was purified by silica gel chromatography (3-6% MeOH in CH2Cl2) to give 2-chloro-5-phenyl-6-[4-({[4-(1,2,3-thiadiazol-4-yl)benzyl]amino}methyl)phenyl]nicotinonitrile (2-6). 1H-NMR (500 MHz, CDCl3) δ 8.63 (s, 1H), 8.01 (d, J=8.0, 2H), 7.98 (s, 1H), 7.47 (d, J=8.1, 2H), 7.28-7.38 (m, 7H), 7.16-7.18 (m, 2H), 3.84 (s, 2H), 3.83 (s, 2H). LRMS m/z (M+H) Calcd: 494.0, found: 494.1.

Workup

  1. concentrationconcentrated
  2. additionThe residue was treated with aqueous Na2CO3 solution (2 M, 10 mL)
  3. extractionextracted with CH2Cl2 (3×30 mL)
  4. customThe combined organic layer was dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography (3-6% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-1258dab66d2d4ca1a736bd5107230272
Source dataset
uspto-grants-2008_08
Patent number
US07414055B2

Reaction notes

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