Piperidine → N-(2-amino-4-{6-[3-hydroxy-3-(1,3-thiazol-2-yl)but-1-yn-1-yl]-1H-indazol-1-yl}pyrimidin-5-yl)-3-methyloxetane-3-carboxamide

HRID 1398496Notes

Reaction equation

HRID 1398496 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14](I)[CH:15]=3)[CH:10]=[N:9]2)[C:5]([NH:18][C:19]([C:21]2([CH3:25])[CH2:24][O:23][CH2:22]2)=[O:20])=[CH:4][N:3]=1.N1CCCCC1.[S: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>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:40]#[C:39][C:37]([OH:41])([C:33]4[S:32][CH:36]=[CH:35][N:34]=4)[CH3:38])[CH:15]=3)[CH:10]=[N:9]2)[C:5]([NH:18][C:19]([C:21]2([CH3:25])[CH2:24][O:23][CH2:22]2)=[O:20])=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 8082PiperidineHCID 582215512-(Thiazol-2-yl)but-3-yn-2-olHCID 68181899N-[2-amino-4-(6-iodo-1H-indazol-1-yl)pyrimidin-5-yl]-3-methyloxetane-3-carboxamide

Product 1

HCID 60164065N-(2-amino-4-{6-[3-hydroxy-3-(1,3-thiazol-2-yl)but-1-yn-1-yl]-1H-indazol-1-yl}pyrimidin-5-yl)-3-methyloxetane-3-carboxamide

Reagents, catalysts & solvents 2

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

Procedure

To a mixture of N-[2-amino-4-(6-iodo-1H-indazol-1-yl)pyrimidin-5-yl]-3-methyloxetane-3-carboxamide (76% purity, 20 mg, 0.034 mmol) and piperidine (0.1 mL) was added tetrakis(triphenylphosphine)palladium (7.8 mg, 0.007 mmol), copper(I) iodide (1.2 mg, 0.007 mmol) and 2-(1,3-thiazol-2-yl)but-3-yn-2-ol (I-1) (10.3 mg, 0.068 mmol). The reaction was purged with N2 and stirred at RT for 2 hr. Reaction mixture was concentrated in vacuo. Purification by flash chromatography (Isolute column, 100% DCM to 2% MeOH-DCM) followed by recrystallization (1:1 MeOH-EtOAc mixture) gave the title compound: 1H NMR (500 MHz, MeOD) δ 1.73 (3H, s), 1.98 (3H, s), 4.47 (2H, d, J=5.99 Hz), 5.01 (2H, d, J=6.15 Hz), 7.43 (1H, dd, J=8.28, 1.18 Hz), 7.57 (1H, d, J=3.31 Hz), 7.79 (1H, d, J=3.31 Hz), 7.83 (1H, d, J=8.35 Hz), 8.39 (1H, s), 8.82 (1H, s), 8.92 (1H, s); m/z=+476.1 (M+H)+.

Workup

  1. customThe reaction was purged with N2
  2. customReaction mixture
  3. concentrationwas concentrated in vacuo
  4. customPurification by flash chromatography (Isolute column, 100% DCM to 2% MeOH-DCM)
  5. customfollowed by recrystallization (1:1 MeOH-EtOAc mixture)

Sources & evidence

ORD record
ord-0eddf92850f841a3b1d60f0a6e0c1421
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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