tert-Butanol → Tert-butyl 3-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzoate

HRID 886996Notes

Reaction equation

HRID 886996 reaction equation
C(O)(C)(C)C.CCN(C(C)C)C(C)C.Cl[C:16]1[C:21]([C:22]([F:25])([F:24])[F:23])=[CH:20][N:19]=[C:18]([NH:26][C:27]2[CH:28]=[C:29]([CH:37]=[CH:38][CH:39]=2)[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[N:17]=1.C(O)(=O)C.[NH2:44][CH2:45][C:46]1[C:47]([N:52]([CH3:57])[S:53]([CH3:56])(=[O:55])=[O:54])=[N:48][CH:49]=[CH:50][CH:51]=1>ClCCCl>[CH3:57][N:52]([S:53]([CH3:56])(=[O:55])=[O:54])[C:47]1[C:46]([CH2:45][NH:44][C:16]2[C:21]([C:22]([F:25])([F:24])[F:23])=[CH:20][N:19]=[C:18]([NH:26][C:27]3[CH:28]=[C:29]([CH:37]=[CH:38][CH:39]=3)[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[N:17]=2)=[CH:51][CH:50]=[CH:49][N:48]=1

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 81531DiisopropylethylamineHCID 57584682Tert-butyl 3-({4-chloro-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzoateHCID 67099950N-(3-(Aminomethyl)pyridin-2-yl)-N-methylmethanesulfonamide acetate

Product 1

HCID 25116907Tert-butyl 3-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzoate

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of tert-butanol (20.0 mL), DCE (20.0 mL) and DIEA (3.13 mL, 18.0 mmol) was treated with C8 (5.60 g, 15.0 mmol) and B5 (5.02 g, 15.0 mmol), and the resulting mixture was stirred at 80° C. under an atmosphere of nitrogen for 16 hours. The mixture was cooled to 25° C. and concentrated. The resultant residue was partitioned between EtOAc and 1 N sodium hydroxide, and the organic phase was collected. The aqueous layer was extracted with EtOAc, and the combined organic phases were dried over MgSO4 and filtered. The resultant filtrate was concentrated under reduced pressure, and the resultant residue was triturated with hot EtOAc to provide 9 as a white solid. Yield: 7.83 grams, 95%. LC/MS (standard) 25°=3.0 min., m/z 553.6 (MH+). HPLC (FAK1) 25°=8.14 min. 1H NMR (d6-DMSO) δ: 9.75 (bs, 1H), 8.44 (d, J=5.2 Hz., 1H), 8.29 (s, 1H), 8.05 (bs, 1H), 7.82 (d, J=7.8 Hz., 1H), 7.60 (t, J=5.7 Hz., 1H), 7.44-7.40 (m, 2H), 7.17 (t, J=5.7 Hz, 1H), 4.82 (d, J=5.7 Hz., 2H), 3.16 (s, 3H), 3.13 (s, 3H), 1.51 (s, 9H) ppm. FAK IC50: 0.0006 μM

Workup

  1. temperatureThe mixture was cooled to 25° C.
  2. concentrationconcentrated
  3. customThe resultant residue was partitioned between EtOAc and 1 N sodium hydroxide
  4. customthe organic phase was collected
  5. extractionThe aqueous layer was extracted with EtOAc
  6. dry with materialthe combined organic phases were dried over MgSO4
  7. filtrationfiltered
  8. concentrationThe resultant filtrate was concentrated under reduced pressure
  9. customthe resultant residue was triturated with hot EtOAc

Sources & evidence

ORD record
ord-c7d1049a3f3345a3bcc62bb6128df397
Source dataset
uspto-grants-2012_08
Patent number
US08247411B2

Reaction notes

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