Triethylamine → Methyl N-[(1S)-2-[[4-[3-iodo-1-(1-methylethyl)-1H-pyrazol-4-yl]-2-pyrimidinyl]amino]-1-methylethyl]carbamate

HRID 1889243Notes

Reaction equation

HRID 1889243 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:9]([I:16])=[N:10][N:11]([CH:13]([CH3:15])[CH3:14])[CH:12]=2)[CH:5]=[CH:4][N:3]=1.[NH2:17][CH2:18][C@@H:19]([NH:21][C:22](=[O:25])[O:23][CH3:24])[CH3:20].C(N(CC)CC)C>C(O)(C)C.O1CCOCC1>[I:16][C:9]1[C:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:17][CH2:18][C@@H:19]([NH:21][C:22](=[O:25])[O:23][CH3:24])[CH3:20])[N:7]=2)=[CH:12][N:11]([CH:13]([CH3:15])[CH3:14])[N:10]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 510343412-Chloro-4-(3-iodo-1-(1-methylethyl)-1H-pyrazol-4-yl)pyrimidineHCID 71721514(S)-methyl 1-aminopropan-2-ylcarbamate

Product 1

HCID 51034342Methyl N-[(1S)-2-[[4-[3-iodo-1-(1-methylethyl)-1H-pyrazol-4-yl]-2-pyrimidinyl]amino]-1-methylethyl]carbamate

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of Intermediate 2-chloro-4-(3-iodo-1-isopropyl-1H-pyrazol-4-yl)pyrimidine (1.4 g, 4.01 mmol), (S)-methyl 1-aminopropan-2-ylcarbamate (0.8 g, 6 mmol) and triethylamine (2.8 ml, 20 mmol) in isopropanol (30 ml) and dioxane (20 mL) was heated in a sealed vessel at 125° C. for 48 hours. The cooled mixture was concentrated under vacuum, and aqueous sodium bicarbonate was added to the residue. The mixture was extracted with ethyl acetate, and the combined extracts were dried over sodium sulfate, filtered, and concentrated. The crude residue was purified by silica gel column chromatography (1:2 hexanes/ethyl acetate eluant) to provide the title compound as a white solid. MS m/z 445.0 (M+1).

Workup

  1. concentrationThe cooled mixture was concentrated under vacuum, and aqueous sodium bicarbonate
  2. additionwas added to the residue
  3. extractionThe mixture was extracted with ethyl acetate
  4. dry with materialthe combined extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified by silica gel column chromatography (1:2 hexanes/ethyl acetate eluant)

Sources & evidence

ORD record
ord-1839d3898b0e42348a5efe1de7dece5d
Source dataset
uspto-grants-2013_08
Patent number
US08501758B2

Reaction notes

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