2-Methyl-3-butyn-2-ol → [1-(2-aminopyrimidin-4-yl)-3-[(dimethylamino)methyl]-1H-indazol-6-yl]-2-methylbut-3-yn-2-ol

HRID 1398485Notes

Reaction equation

Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:18][N:19]([CH3:21])[CH3:20])=[N:7][N:8]2[C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH2:17])[N:12]=2)=[CH:4][CH:3]=1.[CH3:22][C:23]([OH:27])([C:25]#[CH:26])[CH3:24]>N1CCCCC1.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:17][C:13]1[N:12]=[C:11]([N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([CH2:22][C:23]([CH3:24])([OH:27])[C:25]#[CH:26])[CH:10]=3)[C:6]([CH2:18][N:19]([CH3:21])[CH3:20])=[N:7]2)[CH:16]=[CH:15][N:14]=1

Participants

Conditions

Temperature: 75 °C

Procedure

To a solution of 4-{6-bromo-3-[(dimethylamino)methyl]-1H-indazol-1-yl}pyrimidin-2-amine (80 mg, 0.23 mmol) in piperidine (2 mL) was added 2-methyl-but-3-yn-2-ol (38.8 mg, 0.461 mmol), CuI (4.4 mg, 0.023 mmol) and tetrakis(triphenylphosphine)palladium (13.3 mg, 0.012 mmol). The mixture was heated at 75° C. for 1 hr in a sealed tube. Volatiles were removed by concentration in vacuo. Purification by flash chromatography (Isolute column, 100% DCM to 5% MeOH in DCM) afforded the title compound as yellow solid: 1H NMR (500 MHz, DMSO) δ 1.53 (6H, s), 2.23 (6H, s), 3.80 (2H, s), 5.51 (1H, s), 6.93-7.09 (2H, m), 6.97-7.04 (1H, m), 7.32 (1H, d, J=8.20 Hz), 7.93 (1H, s), 8.19-8.35 (1H, m), 8.84 (1H, s); LC-MS: m/z=+351.10 (M+H)+.

Workup

customVolatiles were removed by concentration in vacuo
customPurification by flash chromatography (Isolute column, 100% DCM to 5% MeOH in DCM)

Sources & evidence

ORD record: ord-aff9f1eb1442411da44ec74ad27cff64
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901313B2

Reaction notes

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