Hydrazine hydrate (1:1) → N1-(4-(3-aminophenoxy)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-N4-(1-(2-fluoroethyl)azetidin-3-yl)-2-methoxybenzene-1,4-diamine

HRID 574278Notes

Reaction equation

HRID 574278 reaction equation
C(OC[N:9]1[C:13]2[N:14]=[C:15]([NH:28][C:29]3[CH:34]=[CH:33][C:32]([NH:35][CH:36]4[CH2:39][N:38]([CH2:40][CH2:41][F:42])[CH2:37]4)=[CH:31][C:30]=3[O:43][CH3:44])[N:16]=[C:17]([O:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([N+:25]([O-])=O)[CH:20]=3)[C:12]=2[CH:11]=[CH:10]1)(=O)C(C)(C)C.NN.O>[Pd].CO>[NH2:25][C:21]1[CH:20]=[C:19]([CH:24]=[CH:23][CH:22]=1)[O:18][C:17]1[C:12]2[CH:11]=[CH:10][NH:9][C:13]=2[N:14]=[C:15]([NH:28][C:29]2[CH:34]=[CH:33][C:32]([NH:35][CH:36]3[CH2:39][N:38]([CH2:40][CH2:41][F:42])[CH2:37]3)=[CH:31][C:30]=2[O:43][CH3:44])[N:16]=1

Participants

5

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 86709975(2-(4-(1-(2-fluoroethyl)azetidin-3-ylamino)-2-methoxyphenylamino)-4-(3-nitrophenoxy)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate

Product 1

HCID 86709977N1-(4-(3-aminophenoxy)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-N4-(1-(2-fluoroethyl)azetidin-3-yl)-2-methoxybenzene-1,4-diamineYield 31%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture of (2-(4-(1-(2-fluoroethyl)azetidin-3-ylamino)-2-methoxyphenylamino)-4-(3-nitrophenoxy)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate (530 mg, 0.87 mmol), NH2NH2.H2O (98%, 2.5 mL), Pd/C (110 mg), a magnetite, and MeOH (10 mL) was stirred at reflux temperature overnight. The mixture was cooled to room temperature, and was filtered through diatomaceous earth, washing with MeOH (20 mL). The filtrate was concentrated under reduced pressure. NaHCO3(aq) was added, and the mixture was extracted with ethyl acetate (30 mL×3). The combined organic layers were concentrated under reduced pressure. The crude material was purified by column chromatography (DCM/MeOH=40/1 as elution) to give the title compound (125 mg, yield 31%, M+H+=464.2) as a white solid.

Workup

  1. temperatureat reflux temperature overnight
  2. filtrationwas filtered through diatomaceous earth
  3. washwashing with MeOH (20 mL)
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. additionNaHCO3(aq) was added
  6. extractionthe mixture was extracted with ethyl acetate (30 mL×3)
  7. concentrationThe combined organic layers were concentrated under reduced pressure
  8. customThe crude material was purified by column chromatography (DCM/MeOH=40/1 as elution)

Sources & evidence

ORD record
ord-608df748c4a54a2ab6d4a96c1e7a231b
Source dataset
uspto-grants-2015_05
Patent number
US09034885B2

Reaction notes

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