Sodium hydride → (R)-N-(1-methyl-1H-pyrazol-4-yl)-1-((6-((tetrahydrofuran-2-yl)methoxy)pyridin-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine

HRID 594987Notes

Reaction equation

HRID 594987 reaction equation
[O:1]1[CH2:5][CH2:4][CH2:3][C@@H:2]1[CH2:6][OH:7].[H-].[Na+].F[C:11]1[N:16]=[C:15]([CH2:17][N:18]2[C:22]3=[N:23][C:24]([NH:27][C:28]4[CH:29]=[N:30][N:31]([CH3:33])[CH:32]=4)=[N:25][CH:26]=[C:21]3[CH:20]=[N:19]2)[CH:14]=[CH:13][CH:12]=1>CN(C=O)C>[CH3:33][N:31]1[CH:32]=[C:28]([NH:27][C:24]2[N:23]=[C:22]3[N:18]([CH2:17][C:15]4[CH:14]=[CH:13][CH:12]=[C:11]([O:7][CH2:6][C@H:2]5[CH2:3][CH2:4][CH2:5][O:1]5)[N:16]=4)[N:19]=[CH:20][C:21]3=[CH:26][N:25]=2)[CH:29]=[N:30]1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 6931745(2R)-oxolan-2-ylmethanolHCID 667652621-((6-Fluoropyridin-2-yl)methyl)-N-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine

Product 1

HCID 52913625(R)-N-(1-methyl-1H-pyrazol-4-yl)-1-((6-((tetrahydrofuran-2-yl)methoxy)pyridin-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

(R)-(Tetrahydrofuran-2-yl)methanol (22 mg, 0.214 mmol) was added to a solution of NaH (10 mg, 0.246 mmol) in dry DMF (1 mL) in a 2-necked flask under Nitrogen. Another portion of NaH (10 mg, 0.246 mmol) was added to a stirring solution of 1-((6-fluoropyridin-2-yl)methyl)-N-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine (Example 170) (50 mg, 0.154 mmol) in DMF (1 ml). This solution was added to the 2-necked flask and stirred for 16 h at rt. The reaction was quenched with NH4Cl (sat. solution, 1 mL) and diluted with Ethyl Acetate (20 mL). The organics were separated and washed with NaHCO3 (sat. solution, 20 mL). The aqueous phase was re-extracted with Ethyl Acetate (2×10 mL). The combined organics were dried over Na2SO4, filtered and the solvent evaporated to give a crude product that was purified by prep HPLC. (R)—N-(1-methyl-1H-pyrazol-4-yl)-1-((6-((tetrahydrofuran-2-yl)methoxy)pyridin-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine was obtained as a white solid (24 mg, 38% yield). 1H NMR (d6-Acetone) δ 8.87 (s, 1H), 8.04 (s, 1H), 7.99 (s, 1H), 7.61 (s and t, 2H), 6.70 (d, 1H), 6.64 (d, 1H), 5.54 (s, 2H), 4.07 (m, 3H), 3.82 (s, 3H), 3.75 (m, 1H), 3.61 (m, 1H), 1.84 (m, 3H), 1.54 (m, 1H); LC-MS method B, (ES+) 407.1, RT=7.65 min.

Workup

  1. additionThis solution was added to the 2-necked flask
  2. customThe reaction was quenched with NH4Cl (sat. solution, 1 mL)
  3. additiondiluted with Ethyl Acetate (20 mL)
  4. customThe organics were separated
  5. washwashed with NaHCO3 (sat. solution, 20 mL)
  6. extractionThe aqueous phase was re-extracted with Ethyl Acetate (2×10 mL)
  7. dry with materialThe combined organics were dried over Na2SO4
  8. filtrationfiltered
  9. customthe solvent evaporated
  10. customto give a crude product that
  11. customwas purified by prep HPLC

Sources & evidence

ORD record
ord-a153b2ae95ce47829605bac8c4a0ba9b
Source dataset
uspto-grants-2016_01
Patent number
US09242987B2

Reaction notes

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