Toluene → N-(2-amino-5-(thiophen-2-yl)phenyl)-4-(4-(2,3-dihydropyridin-2-yl)tetrahydropyran-4-yl)benzamide

HRID 415950Notes

Reaction equation

HRID 415950 reaction equation
CO[C:3](=[O:18])[C:4]1[CH:9]=[CH:8][C:7]([C:10]2([C:16]#[N:17])[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:6][CH:5]=1.C([Si](C)(C)C)#C.C(OC(=O)[NH:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2[S:39][CH:40]=[CH:41][CH:42]=2)=[CH:34][C:33]=1[NH2:43])(C)(C)C.[C:45]1(C)[CH:50]=CC=[CH:47][CH:46]=1>[C-]#[O+].[C-]#[O+].[CH-]1C=CC=C1.[Co]>[NH2:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2[S:39][CH:40]=[CH:41][CH:42]=2)=[CH:34][C:33]=1[NH:43][C:3](=[O:18])[C:4]1[CH:5]=[CH:6][C:7]([C:10]2([CH:16]3[CH2:47][CH:46]=[CH:45][CH:50]=[N:17]3)[CH2:11][CH2:12][O:13][CH2:14][CH2:15]2)=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 66111TrimethylsilylacetyleneHCID 57717474tert-Butyl (2-amino-4-(thiophen-2-yl)phenyl)carbamateHCID 666188074-(4-Cyano-tetrahydro-pyran-4-yl)-benzoic acid methyl ester

Product 1

HCID 45101102N-(2-amino-5-(thiophen-2-yl)phenyl)-4-(4-(2,3-dihydropyridin-2-yl)tetrahydropyran-4-yl)benzamide

Reagents, catalysts & solvents 1

HCID 11986239Dicarbonyl(eta5-cyclopentadienyl)cobaltCatalyst

Procedure

To 4-(4-cyano-tetrahydro-pyran-4-yl)-benzoic acid methyl ester (200 mg, 0.81 mmol) in toluene was added ethynyl-trimethyl-silane (800 mg, 10 eq) and CpCo(CO)2 (0.2 eq). The mixture was irradiated with light of 400 nm under stirring conditions for 2 days. Toluene was removed by evaporation. The solids were washed with water and the compound was extracted with EtOAc. The organic phase was dried and evaporated. 4-[4-(4,6-bis-trimethylsilanyl-pyridin-2-yl)-tetrahydro-pyran-4-yl]-benzoic acid methyl ester was dissolved in THF and TBAF was added in excess. The reaction mixture was stirred overnight at room temperature. After the reaction was done, it was extracted with EtOAc. The organic phase was evaporated to be used for next step. Hydrolysis, HATU coupling, and amine de-protection were carried out following the same procedures from Example 64 using (2-amino-4-thiophen-2-yl-phenyl)-carbamic acid tert-butyl ester instead of (3-amino-4′-fluoro-biphenyl-4-yl)-carbamic acid tert-butyl ester. MS found for C27H25N3O2S as (M+H)+ 456.26. 1H NMR (400 MHz, dmso-d6): δ: 9.59 (s, 1H), 8.51 (t, J=4.8 Hz, 1H), 7.87 (d, J=8.4 Hz, 2H), 7.70-7.66 (m, 1H), 7.47 (d, J=8.8 Hz, 2H), 7.39 (d, J=8.8 Hz, 2H), 7.30 (t, J=4.0 Hz, 1H), 7.24 (dd, J=8.4, 6.0 Hz, 1H), 7.18-7.14 (m, 2H), 7.01-6.99 (m, 1H), 6.75 (d, J=8.4 Hz, 1H), 5.09 (s, 2H), 3.64-3.67 (m, 2H), 3.58-3.46 (m, 2H), 2.72-2.69 (m, 2H), 2.34-2.29 (m, 2H).

Workup

  1. customThe mixture was irradiated with light of 400 nm under stirring conditions for 2 days
  2. customToluene was removed by evaporation
  3. washThe solids were washed with water
  4. extractionthe compound was extracted with EtOAc
  5. customThe organic phase was dried
  6. customevaporated
  7. dissolution4-[4-(4,6-bis-trimethylsilanyl-pyridin-2-yl)-tetrahydro-pyran-4-yl]-benzoic acid methyl ester was dissolved in THF
  8. additionTBAF was added in excess
  9. extractionit was extracted with EtOAc
  10. customThe organic phase was evaporated
  11. customHydrolysis, HATU coupling, and amine de-protection

Sources & evidence

ORD record
ord-ed6870f0d00f4cb3b571f4beb9cd51f2
Source dataset
uspto-grants-2012_01
Patent number
US08088771B2

Reaction notes

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