Diisopropylethylamine → HCID 59333959, compound

HRID 331078Notes

Reaction equation

HRID 331078 reaction equation
Cl.Cl.[CH2:3]([O:5][C:6]1[N:11]=[C:10]([NH:12][C:13]2[C:14]3[CH2:25][NH:24][C:23]([CH3:27])([CH3:26])[C:15]=3[N:16](C(OCC)=O)[N:17]=2)[C:9]([F:28])=[CH:8][N:7]=1)[CH3:4].C(N(C(C)C)CC)(C)C.[F:38][C:39]1([C:46](Cl)=[O:47])[CH2:44][CH2:43][N:42]([CH3:45])[CH2:41][CH2:40]1>C1COCC1>[CH2:3]([O:5][C:6]1[N:11]=[C:10]([NH:12][C:13]2[C:14]3[CH2:25][N:24]([C:46]([C:39]4([F:38])[CH2:44][CH2:43][N:42]([CH3:45])[CH2:41][CH2:40]4)=[O:47])[C:23]([CH3:26])([CH3:27])[C:15]=3[NH:16][N:17]=2)[C:9]([F:28])=[CH:8][N:7]=1)[CH3:4]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 210503904-Fluoro-1-methyl-4-piperidinecarbonyl chlorideHCID 68595875HCID 68595875, compound

Product 1

HCID 59333959HCID 59333959, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
65 °C

Procedure

To a solution of ethyl 3-[(2-ethoxy-5-fluoropyrimidin-4-yl)amino]-6,6-dimethyl-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate dihydrochloride (120 mg, 0.27 mmol) in 15 mL THF containing diisopropylethyl amine (0.23 mL, 4 eq) was added a 5 mL THF suspension of 4-fluoro-1-methylpiperidine-4-carbonyl chloride (128 mg, 2.6 eq). After heating for 5 hours at 65° C., the reaction was concentrated to dryness and carried on without further purification. To a solution of ethyl 3-[(2-ethoxy-5-fluoropyrimidin-4-yl)amino]-5-[(4-fluoro-1-methylpiperidin-4-yl)carbonyl]-6,6-dimethyl-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate in methanol was added 2 mL of a 10% sodium hydroxide solution in methanol. After removing the solvent in vacuo, the residue was purified as in Example K1 above. See Table 1 below for NMR data.

Workup

  1. additionwas added
  2. concentrationthe reaction was concentrated to dryness
  3. customcarried on without further purification
  4. additionTo a solution of ethyl 3-[(2-ethoxy-5-fluoropyrimidin-4-yl)amino]-5-[(4-fluoro-1-methylpiperidin-4-yl)carbonyl]-6,6-dimethyl-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate in methanol was added 2 mL of a 10% sodium hydroxide solution in methanol
  5. customAfter removing the solvent in vacuo

Sources & evidence

ORD record
ord-8cfbbd3c40a3480c9699f8f094bfd9ef
Source dataset
uspto-grants-2014_11
Patent number
US08877761B2

Reaction notes

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