Piperidine → 4-[1-(2-aminopyrimidin-4-yl)-3-[(morpholin-4-yl)carbonyl]-1H-indazol-6-yl]-2-(1,3-oxazol-2-yl)but-3-yn-2-ol

HRID 1398583Notes

Reaction equation

HRID 1398583 reaction equation
I[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:18]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[O:19])=[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.N1CCCCC1.[O:32]1[CH:36]=[CH:35][N:34]=[C:33]1[C:37]([OH:41])([C:39]#[CH:40])[CH3:38]>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.[Cu]I>[NH2:17][C:13]1[N:12]=[C:11]([N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([C:40]#[C:39][C:37]([C:33]4[O:32][CH:36]=[CH:35][N:34]=4)([OH:41])[CH3:38])[CH:10]=3)[C:6]([C:18]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[O:19])=[N:7]2)[CH:16]=[CH:15][N:14]=1

Participants

6

Reactant 3

HCID 8082PiperidineHCID 681816904-{6-Iodo-3-[(morpholin-4-yl)carbonyl]indazol-1-yl}pyrimidin-2-amineHCID 866695942-(1,3-Oxazol-2-yl)but-3-yn-2-ol

Product 1

HCID 681816724-[1-(2-aminopyrimidin-4-yl)-3-[(morpholin-4-yl)carbonyl]-1H-indazol-6-yl]-2-(1,3-oxazol-2-yl)but-3-yn-2-olYield 40.9%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
35 °C

Procedure

To a pressure tube was added 4-{6-iodo-3-[(morpholin-4-yl)carbonyl]-1H-indazol-1-yl}pyrimidin-2-amine (150 mg, 0.33 mmol) followed by piperidine (2.0 mL), tetrakis(triphenylphosphine)palladium(0) (38.5 mg, 0.03 mmol), copper(I) iodide (6.35 mg, 0.03 mmol) and 2-(1,3-oxazol-2-yl)but-3-yn-2-ol (68.53 mg, 0.5 mmol). The reaction was capped and stirred at 35° C. for 2.5 hr. The reaction mixture was concentrated in vacuo. DCM (5 mL×2) added and the mixture was concentrated in vacuo. Purification by column chromatography (1% to 10% MeOH in DCM), followed by trituration with a mixture of MeCN/diethyl ether mixture (3/1) gave the title compound as an off-white solid (62 mg): 1H NMR (500 MHz, DMSO) delta 3.67 (2H, d, J=4.26 Hz), 3.75 (4H, d, J=5.67 Hz), 3.94 (2H, d, J=3.94 Hz), 4.06 (3H, s), 6.72-6.89 (1H, m), 6.93-7.33 (4H, m), 7.45 (1H, d, J=7.57 Hz), 8.04 (1H, d, J=7.88 Hz), 8.11-8.23 (1H, m), 8.97 (1H, s); LC-MS: m/z=+460.15 (M+H)+.

Workup

  1. customThe reaction was capped
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. additionDCM (5 mL×2) added
  4. concentrationthe mixture was concentrated in vacuo
  5. customPurification by column chromatography (1% to 10% MeOH in DCM)
  6. additionfollowed by trituration with a mixture of MeCN/diethyl ether mixture (3/1)

Sources & evidence

ORD record
ord-38b84c49ba3743cda75e48d0852854ac
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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