Dimethylformamide → HCID 178484485, compound

HRID 2200805Notes

Reaction equation

HRID 2200805 reaction equation
[CH:1]([N:4](CC)[CH:5](C)C)(C)C.[C:10]([CH2:12][C:13]1([N:37]2[CH:41]=[C:40]([C:42]3[C:43]4[CH:50]=[CH:49][N:48](COCC[Si](C)(C)C)[C:44]=4[N:45]=[CH:46][N:47]=3)[CH:39]=[N:38]2)[CH2:16][N:15]([C@@H:17]2[CH2:22][CH2:21][C@H:20]([O:23][C:24]3[N:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[N:27]=[C:26]([C:34]([OH:36])=O)[CH:25]=3)[CH2:19][CH2:18]2)[CH2:14]1)#[N:11].F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)[O:69]N1C2N=CC=CC=2N=N1.Cl.CNC.CN(C)[CH:89]=[O:90]>>[F:31][C:30]([F:33])([F:32])[C:89]([OH:90])=[O:69].[F:31][C:30]([F:33])([F:32])[C:89]([OH:90])=[O:69].[C:10]([CH2:12][C:13]1([N:37]2[CH:41]=[C:40]([C:42]3[C:43]4[CH:50]=[CH:49][NH:48][C:44]=4[N:45]=[CH:46][N:47]=3)[CH:39]=[N:38]2)[CH2:16][N:15]([C@@H:17]2[CH2:18][CH2:19][C@H:20]([O:23][C:24]3[N:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[N:27]=[C:26]([C:34]([N:4]([CH3:5])[CH3:1])=[O:36])[CH:25]=3)[CH2:21][CH2:22]2)[CH2:14]1)#[N:11]

Participants

6

Reactant 5

HCID 6228Dimethylformamide2×HCID 10473Dimethylamine, hydrochlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178504215HCID 178504215, compound

Product 1

HCID 178484485HCID 178484485, compound

Procedure

N,N-Diisopropylethylamine (10.31 μL, 0.05920 mmol) and 6-[(cis-4-{3-(cyanomethyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}cyclohexyl)oxy]-2-(trifluoromethyl)pyrimidine-4-carboxylic acid (20.00 mg, 0.02866 mmol) were dissolved in N,N-dimethylformamide (0.53 mL) and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (19.60 mg, 0.05154 mmol) in N,N-dimethylformamide (1.00 mL) was added. The reaction mixture was stirred for 10 minutes and dimethylamine hydrochloride (6.09 mg, 0.0747 mmol) was added. The reactions were stirred at 25° C. overnight at which time LCMS analysis showed that the reaction was mostly complete and was purified by LC and evaporated and deprotected as in Example 1 (CH2Cl2/TFA; MeOH/NH4OH) and purified to give the product. 1H NMR (300 MHz, CD3OD) δ 9.11 (s, 1H), 8.90 (s, 1H), 8.60 (s, 1H), 7.82 (d, 114), 7.28 (d, 1H), 7.18 (s, 1H), 5.52 (m, 1H), 5.10 (d, 2H), 4.90 (d, 2H), 3.74 (s, 2H), 3.53 (m, 1H), 3.12 and 3.04 (2 s, 3H), 2.30 (m, 2H), 2.03 (m, 2H), 1.75 (m, 4H). MS (ES): 595(M+1).

Workup

  1. stirringThe reactions were stirred at 25° C. overnight at which time LCMS analysis
  2. customwas purified by LC
  3. customevaporated
  4. custompurified
  5. customto give the product

Sources & evidence

ORD record
ord-1d1cbf1e88994a15b7a241db4cbaadf1
Source dataset
uspto-grants-2016_06
Patent number
US09359358B2

Reaction notes

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