Phthalamide → 4-(4-(aminomethyl)-4-fluoropiperidin-1-yl)-N-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-6-yl)furo[3,2-d]pyrimidin-2-amine

HRID 1038821Notes

Reaction equation

HRID 1038821 reaction equation
[F:1][C:2]1([CH2:35][N:36]2C(=O)C3C(=CC=CC=3)C2=O)[CH2:7][CH2:6][N:5]([C:8]2[C:9]3[O:34][CH:33]=[CH:32][C:10]=3[N:11]=[C:12]([NH:14][C:15]3[CH:23]=[C:22]4[C:18]([CH:19]=[N:20][N:21]4[CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])=[CH:17][CH:16]=3)[N:13]=2)[CH2:4][CH2:3]1.C(N)(=O)C1C(=CC=CC=1)C(N)=O.ClC1N=C(Cl)C2OC=CC=2N=1.C[Si](C)(C)CCOCN1C2C(=CC=C(N)C=2)C=N1.O.NN>CO>[NH2:36][CH2:35][C:2]1([F:1])[CH2:7][CH2:6][N:5]([C:8]2[C:9]3[O:34][CH:33]=[CH:32][C:10]=3[N:11]=[C:12]([NH:14][C:15]3[CH:23]=[C:22]4[C:18]([CH:19]=[N:20][N:21]4[CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:29])[CH3:30])=[CH:17][CH:16]=3)[N:13]=2)[CH2:4][CH2:3]1

Participants

7

Reactant 5

HCID 6956PhthalamideHCID 24654Hydrazine hydrate (1:1)HCID 457899682,4-Dichlorofuro[3,2-D]pyrimidineHCID 67293196HCID 67293196, compound2×HCID 687527592-((4-fluoro-1-(2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-6-ylamino)furo[3,2-d]pyrimidin-4-yl)piperidin-4-yl)methyl)isoindoline-1,3-dione

Product 1

HCID 687487904-(4-(aminomethyl)-4-fluoropiperidin-1-yl)-N-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-6-yl)furo[3,2-d]pyrimidin-2-amineYield 100%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 2-((4-fluoro-1-(2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-6-ylamino)furo[3,2-d]pyrimidin-4-yl)piperidin-4-yl)methyl)isoindoline-1,3-dione (0.510 g, 0.795 mmol, prepared using W from Preparation #X.1, V, U with phthalamide, G, A with 2,4-dichlorofuro[3,2-d]pyrimidine [ArkPharm] and B with 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-6-amine [WO 2010/027500 Intermediate 21, Step C]) in MeOH (20 mL) was treated with hydrazine hydrate (0.190 mL, 2.50 mmol). The mixture was heated at about 70° C. for about 3 h. The mixture was cooled to rt and concentrated in vacuo. The residue was dissolved in DCM/MeOH (10:1) (30 mL) and stirred for about 30 min. The resulting suspension was filtered and the filtrate was concentrated in vacuo to give 4-(4-(aminomethyl)-4-fluoropiperidin-1-yl)-N-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-6-yl)furo[3,2-d]pyrimidin-2-amine (0.41 g, 100%). LC/MS (Table 2, Method i) Rt=1.60 min; MS m/z 512 (M+H)+.

Workup

  1. customprepared
  2. temperatureThe mixture was cooled to rt
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in DCM/MeOH (10:1) (30 mL)
  5. filtrationThe resulting suspension was filtered
  6. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-20035604c5e546c7a11e72ed317802a2
Source dataset
uspto-grants-2013_10
Patent number
US08551981B2

Reaction notes

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