N-Methylbenzeneethanamine → (S)-5-(4-aminophenylthio)-4-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)-N-(2-phenylpropyl)thiophene-2-carboxamide

HRID 883997Notes

Reaction equation

HRID 883997 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[S:13][C:12]([C:14](O)=[O:15])=[CH:11][C:10]=2[NH:17][C:18]2[C:19]3[CH:27]=[CH:26][C:25]([CH:28]([CH3:30])[CH3:29])=[N:24][C:20]=3[N:21]=[CH:22][N:23]=2)=[CH:4][CH:3]=1.C[NH:32][CH2:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.[CH:41](N(CC)C(C)C)(C)C.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CS(C)=O.O>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[S:13][C:12]([C:14]([NH:32][CH2:33][C@H:34]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH3:41])=[O:15])=[CH:11][C:10]=2[NH:17][C:18]2[C:19]3[CH:27]=[CH:26][C:25]([CH:28]([CH3:30])[CH3:29])=[N:24][C:20]=3[N:21]=[CH:22][N:23]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 11503N-MethylbenzeneethanamineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 670411655-(4-Aminophenylthio)-4-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)thiophene-2-carboxylic acid

Product 1

HCID 25117305(S)-5-(4-aminophenylthio)-4-(7-isopropylpyrido[2,3-d]pyrimidin-4-ylamino)-N-(2-phenylpropyl)thiophene-2-carboxamideYield 85.2%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

The product of Example 90F (62 mg, 0.142 mmol) in dimethyl sulfoxide (2 mL) under a nitrogen atmosphere was reacted with (S)-(−)-□-methylphenethylamine (23 mg, 0.170 mmol), N,N-diisopropylethylamine (0.123 mL, 0.708 mmol), and O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (55 mg, 0.170 mmol at room temperature for 20 hours. The reaction mixture was diluted with water (10 mL), and extracted with ethyl acetate (50 mL). The organic extract was washed sequentially with water (3×10 mL), saturated aqueous sodium hydrogencarbonate (20 mL), and brine (20 mL), dried over magnesium sulfate, filtered, and concentrated by rotary evaporation. Purification of the residue by silica gel flash chromatography eluting with 4:96 methanol/methylene chloride afforded the title compound (67 mg, 0.121 mmol, 85%). 1H NMR (300 MHz, DMSO-D6) δ ppm 1.19 (d, J=6.99 Hz, 3 H) 1.33 (d, J=6.99 Hz, 6 H) 2.91-3.07 (m, 1 H) 3.14-3.29 (m, 1 H) 5.50 (s, 2 H) 6.51 (d, J=8.46 Hz, 2 H) 7.12 (d, J=8.82 Hz, 2 H) 7.16-7.34 (m, 5 H) 7.63 (d, J=8.46 Hz, 1 H) 7.77 (s, 1 H) 8.50 (t, J=5.88 Hz, 1 H) 8.62 (s, 1 H) 8.82 (d, J=8.82 Hz, 1 H) 9.97 (s, 1 H); MS (ESI+) m/z 555 (M+H)+, 1109 (2M+H)+, MS (ESI−) m/z 553 (M−H)−.

Workup

  1. extractionextracted with ethyl acetate (50 mL)
  2. extractionThe organic extract
  3. washwas washed sequentially with water (3×10 mL), saturated aqueous sodium hydrogencarbonate (20 mL), and brine (20 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation
  7. customPurification of the residue by silica gel flash chromatography
  8. washeluting with 4:96 methanol/methylene chloride

Sources & evidence

ORD record
ord-d5fac575de2d45b88295485372b41971
Source dataset
uspto-grants-2012_08
Patent number
US08236950B2

Reaction notes

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