Acetonitrile--water (1/1) → HCID 178509203, compound

HRID 40979Notes

Reaction equation

HRID 40979 reaction equation
C[Si](C)(C)CCOC[N:7]1[C:11]2[N:12]=[CH:13][N:14]=[C:15]([C:16]3[CH:17]=[N:18][N:19]([C@@H:21]4[CH2:26][CH2:25][C@H:24]([CH2:27][S:28][C:29]5[NH:30][C:31]([NH2:34])=[N:32][N:33]=5)[CH2:23][CH2:22]4)[CH:20]=3)[C:10]=2[CH:9]=[CH:8]1.CC#N.O>C(O)(C(F)(F)F)=O>[N:12]1[C:11]2[NH:7][CH:8]=[CH:9][C:10]=2[C:15]([C:16]2[CH:17]=[N:18][N:19]([C@@H:21]3[CH2:26][CH2:25][C@H:24]([CH2:27][S:28][C:29]4[NH:30][C:31]([NH2:34])=[N:32][N:33]=4)[CH2:23][CH2:22]3)[CH:20]=2)=[N:14][CH:13]=1

Participants

4

Reactant 2

HCID 18373917Acetonitrile--water (1/1)HCID 178504222HCID 178504222, compound

Product 1

HCID 178509203HCID 178509203, compound

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

5-[(cis-4-[4-(7-[2-(Trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclohexylmethyl)thio]-4H-1,2,4-triazol-3-amine (9a) was dissolved in TFA (1 mL) and was stirred for 2 h. The solution was concentrated using a rotary evaporator to remove TFA. The residue was dissolved in methanol (1 mL) and ammonium hydroxide (1 mL) added. The solution was stirred overnight. LCMS showed complete de-protection. The solution was concentrated using a rotary evaporator. The product was isolated by prep LCMS using a 30 mm×100 mm C18 column; 11% CH3CN—H2O (0.1% TFA), 1.5 min, to 33% at 6 min; 60 mL/min; detector set at m/z 396; retention time, 5.5 min (2 runs). The eluate was freeze dried. Yield 21 mg (di-TFA salt). LC/MS (M+H)+: 396, 1H NMR (d6-DMSO) δ 12.9 (br s, 1H, NH); 8.9 (2 singlets, 2H); 8.5 (s, 1H); 7.9 (m, 1H); 7.3 (m, 1H); 4.4 (m, 1H, NCH); 3.1 (d, 2H); 2.2 (m, 2H); 1.9 (m, 3H); 1.7 (m, 2H); 1.6 (m, 2H). MS (ES) 396 (M+1).

Workup

  1. concentrationThe solution was concentrated
  2. customa rotary evaporator
  3. customto remove TFA
  4. dissolutionThe residue was dissolved in methanol (1 mL)
  5. additionammonium hydroxide (1 mL) added
  6. stirringThe solution was stirred overnight
  7. concentrationThe solution was concentrated
  8. customa rotary evaporator
  9. customThe product was isolated by prep LCMS
  10. customretention time, 5.5 min (2 runs)
  11. customdried

Sources & evidence

ORD record
ord-84d9838b69724ed5ad833608089b1820
Source dataset
uspto-grants-2013_09
Patent number
US08530485B2

Reaction notes

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