Dimethylformamide → HCID 58972740, compound

HRID 1485361Notes

Reaction equation

HRID 1485361 reaction equation
[H-].[Na+].[CH3:3][C:4]1([CH3:11])[O:8][CH:7]([CH2:9][OH:10])[CH2:6][O:5]1.CN(C=O)C.CS([C:21]1[N:22]=[C:23]([NH:42][C:43]2[CH:48]=[CH:47][C:46]([C:49]([F:52])([F:51])[F:50])=[CH:45][CH:44]=2)[C:24]2[CH2:30][CH2:29][N:28]([C:31]3[C:36]([C:37]([F:40])([F:39])[F:38])=[CH:35][CH:34]=[CH:33][N:32]=3)[CH2:27][CH2:26][C:25]=2[N:41]=1)(=O)=O>CO>[CH3:3][C:4]1([CH3:11])[O:8][C@@H:7]([CH2:9][O:10][C:21]2[N:22]=[C:23]([NH:42][C:43]3[CH:48]=[CH:47][C:46]([C:49]([F:52])([F:50])[F:51])=[CH:45][CH:44]=3)[C:24]3[CH2:30][CH2:29][N:28]([C:31]4[C:36]([C:37]([F:40])([F:39])[F:38])=[CH:35][CH:34]=[CH:33][N:32]=4)[CH2:27][CH2:26][C:25]=3[N:41]=2)[CH2:6][O:5]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 7528SolketalHCID 24758Sodium hydrideHCID 58972737HCID 58972737, compound

Product 1

HCID 58972740HCID 58972740, compoundYield 71.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

A dispersion of NaH in mineral oil (12.0 mg, 0.28 mmol) was added to a flask containing (2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (116 μL, 0.94 mmol) and DMF (1.0 mL). After 30 min, the mixture was transferred to a flask containing [2-methanesulfonyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl]-(4-trifluoromethyl-phenyl)-amine (Example 53; 50 mg, 0.094 mmol). The resulting mixture was then heated at 70° C. for 24 h. The mixture was cooled, diluted with MeOH (1.0 mL) and purified by reverse phase HPLC, yielding 39 mg (70%) of the title compound. MS (ESI): mass calcd. for C27H27F6N5O3, 583.20; m/z found, 584.2 [M+H]+. 1H NMR (CDCl3): 8.39-8.37 (m, 1H), 7.89-7.86 (m, 1H), 7.69 (d, J=11.0 Hz, 2H), 7.59 (d, J=11.0 Hz, 2H), 6.98-6.94 (m, 1H), 6.68 (s, 1H), 4.52-4.56 (m, 1H), 4.42-4.38 (m, 1H), 4.28-4.24 (m, 1H), 4.16-4.12 (m, 1H), 3.94-3.90 (m, 1H), 3.63-3.56 (m, 4H), 3.18-3.15 (m, 2H), 2.96-2.93 (m, 2H), 1.46 (s, 3H), 1.38 (s, 3H).

Workup

  1. customthe mixture was transferred to a flask
  2. temperatureThe mixture was cooled
  3. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-13fa9b0cc06a49aa9b08e7fa3d2e1d9e
Source dataset
uspto-grants-2016_08
Patent number
US09422293B2

Reaction notes

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