Water → N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-((6-fluoro-1H-pyrrolo[3,2-b]pyridin-5-yl)methyl)-N2-methylpyrimidine-2,4-diamine

HRID 2409078Notes

Reaction equation

HRID 2409078 reaction equation
[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[CH:15]=[CH:14][N:13]=[C:12]([N:16]([CH2:18][C:19]4[N:24]=[C:23]5[CH:25]=[CH:26][N:27](COCC[Si](C)(C)C)[C:22]5=[CH:21][C:20]=4[F:36])[CH3:17])[N:11]=3)[CH:5]=2)[CH2:3][CH2:2]1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O.[NH4+].[OH-]>C1COCC1>[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[CH:15]=[CH:14][N:13]=[C:12]([N:16]([CH2:18][C:19]4[N:24]=[C:23]5[CH:25]=[CH:26][NH:27][C:22]5=[CH:21][C:20]=4[F:36])[CH3:17])[N:11]=3)[CH:5]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 962WaterHCID 14923Ammonium HydroxideHCID 2724141Tetrabutylammonium FluorideHCID 86762628N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-((6-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[3,2-b]pyridin-5-yl)methyl)-N2-methylpyrimidine-2,4-diamine

Product 1

HCID 71600008N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-((6-fluoro-1H-pyrrolo[3,2-b]pyridin-5-yl)methyl)-N2-methylpyrimidine-2,4-diamineYield 20%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
63 °C

Procedure

A mixture of N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-((6-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[3,2-b]pyridin-5-yl)methyl)-N2-methylpyrimidine-2,4-diamine (40 mg, 0.1 mmol) and tetrabutyl ammonium fluoride (260 mg, 1 mmol) in THF (5 mL) was heated at 63° C. for 18 h. The reaction mixture was poured into water (10 mL) and the pH was adjusted to 10 by addition of an NH4OH solution. The mixture was extracted with EtOAc (50 mL×3) and the combined extracts dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified by reverse phase preparative HPLC to afford 8 mg, (20%) of N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-((6-fluoro-1H-pyrrolo[3,2-b]pyridin-5-yl)methyl)-N2-methylpyrimidine-2,4-diamine as a white solid. 1H NMR (500 MHz, DMSO) δ 11.8 (brs, 1H), 11.3 (brs, 1H), 9.33 (brs, 1H), 7.85 (d, J=5 Hz, 1H), 7.65 (d, 0.1=10 Hz, 1H), 7.58 (d, J=3 Hz, 1H), 6.51 (s, 1H), 6.00-6.20 (brs, 2H), 5.06 (s, 2H), 3.16 (s, 3H), 1.81 (s, 1H), 0.85 (s, 2H), 0.59 (s, 2H); MS (ESI): m/z=379.3 [M+1]+.

Workup

  1. extractionThe mixture was extracted with EtOAc (50 mL×3)
  2. dry with materialthe combined extracts dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-42b5918875d84f5a93559af08fd8821d
Source dataset
uspto-grants-2014_08
Patent number
US08815877B2

Reaction notes

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