Dimethylformamide → HCID 89964943, compound

HRID 1846217Notes

Reaction equation

HRID 1846217 reaction equation
C1N=CN([C:6](N2C=NC=C2)=[O:7])C=1.[F:13][C:14]([F:19])([F:18])[C@@H:15]([NH2:17])[CH3:16].[F:20][C:21]([F:40])([F:39])[C:22]1[CH:27]=[CH:26][C:25]([C:28]2([NH2:38])[C:33]3=[N:34][CH:35]=[CH:36][CH:37]=[C:32]3[O:31][CH2:30][CH2:29]2)=[CH:24][CH:23]=1.CCN(C(C)C)C(C)C.CN([CH:53]=[O:54])C>C(Cl)Cl>[F:13][C:14]([F:19])([F:18])[C:53]([OH:54])=[O:31].[F:40][C:21]([F:20])([F:39])[C:22]1[CH:23]=[CH:24][C:25]([C@:28]2([NH:38][C:6]([NH:17][C@@H:15]([CH3:16])[C:14]([F:19])([F:18])[F:13])=[O:7])[C:33]3=[N:34][CH:35]=[CH:36][CH:37]=[C:32]3[O:31][CH2:30][CH2:29]2)=[CH:26][CH:27]=1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 10964447(S)-1,1,1-trifluoropropan-2-amineHCID 89964678HCID 89964678, compound

Product 1

HCID 89964943HCID 89964943, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of CDI (41.3 mg, 0.255 mmol) in DCM (0.25 mL) was added (S)-1,1,1-trifluoropropan-2-amine (0.026 mL, 0.255 mmol). The round bottom flask was then sealed, and the mixture was stirred at room temperature for 2.5 h. A solution of 4-(4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-pyrano[3,2-b]pyridin-4-amine (50.0 mg, 0.170 mmol) and DIEA (0.058 mL, 0.340 mmol) in DCM (1 mL) was then added, and the reaction was stirred at room temperature for 20 h. The reaction was diluted with DMF, filtered through a syringe filter, and the reaction purified by RPHPLC (Gemini Axia C18 50×150 mm column, gradient elution 10-100% MeCN/0.1% TFA in H2O). The product containing fractions were combined and the solvent removed by lyophilization to give the title compound as a white solid. MS (ESI, positive ion) m/z: 433.9 (MH+). 1H NMR (300 MHz, d4-MeOH) δ: 8.18-8.29 (m, 1H), 7.64-7.71 (m, J=8.2 Hz, 2H), 7.59 (br. s., 1H), 7.47-7.56 (m, 1H), 7.34-7.47 (m, J=8.3 Hz, 2H), 4.25-4.46 (m, 2H), 4.06 (ddd, J=11.9, 9.6, 2.6 Hz, 1H), 3.02-3.20 (m, 1H), 2.54-2.72 (m, 1H), 1.19-1.30 (m, 3H).

Workup

  1. customThe round bottom flask was then sealed
  2. stirringthe reaction was stirred at room temperature for 20 h
  3. filtrationfiltered through a syringe
  4. filtrationfilter
  5. customthe reaction purified by RPHPLC (Gemini Axia C18 50×150 mm column, gradient elution 10-100% MeCN/0.1% TFA in H2O)
  6. additionThe product containing fractions
  7. customthe solvent removed by lyophilization

Sources & evidence

ORD record
ord-854cd606bcde438792308139210741d2
Source dataset
uspto-grants-2015_02
Patent number
US08952009B2

Reaction notes

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