4-{6-Iodo-3-[(morpholin-4-yl)carbonyl]indazol-1-yl}pyrimidin-2-amine → (2S)-4-[1-(2-aminopyrimidin-4-yl)-3-[(morpholin-4-yl)carbonyl]-1H-indazol-6-yl]-2-(pyrimidin-2-yl)but-3-yn-2-ol

HRID 1398589Notes

Reaction equation

HRID 1398589 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.[N:26]1[CH:31]=[CH:30][CH:29]=[N:28][C:27]=1[C@@:32]([OH:36])([C:34]#[CH:35])[CH3:33]>C(N(CC)CC)C.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:35]#[C:34][C@@:32]([C:27]4[N:26]=[CH:31][CH:30]=[CH:29][N:28]=4)([OH:36])[CH3:33])[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 2

HCID 681816904-{6-Iodo-3-[(morpholin-4-yl)carbonyl]indazol-1-yl}pyrimidin-2-amineHCID 86669596(2S)-2-(pyrimidin-2-yl)but-3-yn-2-ol

Product 1

HCID 68181727(2S)-4-[1-(2-aminopyrimidin-4-yl)-3-[(morpholin-4-yl)carbonyl]-1H-indazol-6-yl]-2-(pyrimidin-2-yl)but-3-yn-2-ol

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8471TriethylamineSolvent

Procedure

To solution of 4-{6-iodo-3-[(morpholin-4-yl)carbonyl]-1H-indazol-1-yl}pyrimidin-2-amine (60 mg, 0.13 mmol) in triethylamine (2 mL) was introduced tetrakis(triphenylphosphine)palladium (0) (15.4 mg, 0.01 mmol), copper(I) iodide (2.5 mg, 0.01 mmol) and (2S)-2-(pyrimidin-2-yl)but-3-yn-2-ol (30 mg, 0.20 mmol). After 18 hr at RT, the reaction mixture was concentrated in vacuo, DCM (10 mL) was added and the solution re-evaporated to dryness in vacuo (re-evaporation process repeated twice). Purification of the residue by column chromatography (Biotage, DCM containing a 0-10% gradient of methanol) furnished the title compound as an off-white solid: 1H NMR (500 MHz, DMSO-d6) delta 1.79-2.05 (3H, m), 3.59-3.68 (2H, m), 3.71-3.79 (4H, m), 3.89-4.01 (2H, m), 6.17-6.37 (1H, m), 6.98-7.10 (1H, m), 7.12-7.27 (2H, m), 7.32-7.42 (1H, m), 7.47-7.58 (1H, m), 7.92-8.05 (1H, m), 8.26-8.39 (1H, m), 8.80-9.04 (3H, m); LC-MS: m/z=+471.05 (M+H)+.

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo, DCM (10 mL)
  2. additionwas added
  3. customthe solution re-evaporated to dryness in vacuo (
  4. customre-evaporation process
  5. customPurification of the residue by column chromatography (Biotage, DCM containing a 0-10% gradient of methanol)

Sources & evidence

ORD record
ord-928cb2f480ae479a8de4076d4239bdda
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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