Sodium hydride → HCID 68181837, compound

HRID 1398602Notes

Reaction equation

HRID 1398602 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:14])([CH3:13])[CH3:12])=[N:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:18]1[CH:23]=[CH:22][N:21]=[C:20]([NH2:24])[N:19]=1>CN(C=O)C>[NH2:24][C:20]1[N:21]=[C:22]([N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([Br:1])[CH:10]=3)[C:6]([C:11]([OH:14])([CH3:12])[CH3:13])=[N:7]2)[CH:23]=[CH:18][N:19]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2233322-Amino-4-chloropyrimidineHCID 178458960HCID 178458960, compound

Product 1

HCID 68181837HCID 68181837, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(6-bromo-1H-indazol-3-yl)propan-2-ol (317 mg, 1.24 mmol) in DMF (10 mL) was added NaH (60% oil dispersion, 79.5 mg, 1.99 mmol) at 0° C. The reaction mixture was stirred at RT for 20 minutes before addition of 4-chloropyrimidin-2-amine (321.95 mg, 2.49 mmol). The mixture was stirred at RT for 10 minutes and then at 65° C. for 23 hr. The reaction mixture was quenched by addition of water (10 mL) and EtOAc (2 mL) was added. The resultant precipitate was collected by suction filtration and then thoroughly dried under high vacuum and triturated from diethyl ether. The crude product was purified by flash chromatography (Biotage, 1-5% methanol in DCM) to give the title intermediate as a pale yellow solid: 1H NMR (500 MHz, DMSO) delta 1.63 (6 H, s), 5.59 (1H, s), 7.23-6.93 (3H, m), 7.49 (1H, dd, J=8.6, 1.5 Hz), 8.07 (1H, d, J=8.6 Hz), 8.27 (1H, d, J=5.5 Hz), 9.11 (1H, d, J=1.4 Hz); LC-MS m/z=+347.95/349.80 (M+H)+.

Workup

  1. waitat 65° C. for 23 hr
  2. customThe reaction mixture was quenched by addition of water (10 mL) and EtOAc (2 mL)
  3. additionwas added
  4. filtrationThe resultant precipitate was collected by suction filtration
  5. customthoroughly dried under high vacuum
  6. customtriturated from diethyl ether
  7. customThe crude product was purified by flash chromatography (Biotage, 1-5% methanol in DCM)

Sources & evidence

ORD record
ord-c9550edc82854922aafeb5c4d74f4ea7
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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