Hydrochloric Acid → N4-[3-Fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]-6-(piperazin-1-yl-carbonyl)pyrimidine-2,4-diamine

HRID 16452Notes

Reaction equation

HRID 16452 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]([O:10]C)=O)[CH:5]=[C:4]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][C:20]3[CH:25]=[CH:24][N:23]=[C:22]4[NH:26][CH:27]=[CH:28][C:21]=34)=[C:15]([F:29])[CH:14]=2)[N:3]=1.[OH-].[Na+].Cl.CN(C(ON1N=[N:48][C:43]2C=[CH:45][CH:46]=[N:47][C:42]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=NC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.N1CCNCC1>O>[F:29][C:15]1[CH:14]=[C:13]([NH:12][C:4]2[CH:5]=[C:6]([C:8]([N:47]3[CH2:42][CH2:43][NH:48][CH2:45][CH2:46]3)=[O:10])[N:7]=[C:2]([NH2:1])[N:3]=2)[CH:18]=[CH:17][C:16]=1[O:19][C:20]1[CH:25]=[CH:24][N:23]=[C:22]2[NH:26][CH:27]=[CH:28][C:21]=12

Participants

9

Reactant 7

HCID 313Hydrochloric AcidHCID 4837PiperazineHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 17979310Methyl 2-amino-6-{[3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]amino}-pyrimidine-4-carboxylate

Product 1

HCID 58733364N4-[3-Fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]-6-(piperazin-1-yl-carbonyl)pyrimidine-2,4-diamine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

0.072 g (0.18 mmol) of methyl 2-amino-6-{[3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yl-oxy)phenyl]amino}pyrimidine-4-carboxylate (from example 53) is suspended in 3 ml of water. 0.9 ml of a 1 molar sodium hydroxide solution is added. The reaction mixture is stirred at 100° C. for 18 hours. After cooling, the mixture is adjusted to pH 4.5 using 0.95 ml of a 1N hydrochloric acid solution. The precipitate formed is filtered off with suction and dried. The solid is suspended in DMF. 0.066 mg (0.175 mmol) of HATU, 0.025 g (0.184 mmol) of HOAT, 0.064 ml (0.368 mmol) of diisopropylethylamine and 0.031 g (0.368 mmol) of piperazine are added successively. The reaction mixture is stirred at 40° C. for 5 hours. After cooling, the solution is purified by preparative HPLC. This gives 0.012 g (15% of theory) of product.

Workup

  1. temperatureAfter cooling
  2. customThe precipitate formed
  3. filtrationis filtered off with suction
  4. customdried
  5. stirringThe reaction mixture is stirred at 40° C. for 5 hours
  6. temperatureAfter cooling
  7. customthe solution is purified by preparative HPLC

Sources & evidence

ORD record
ord-f71f7eb3860c4234856e6b14125240ea
Source dataset
uspto-grants-2010_06
Patent number
US07737153B2

Reaction notes

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