Triethylamine → N-[2-amino-4-(6-cyano-1H-indazol-1-yl)pyrimidin-5-yl]-3-methyloxetane-3-carboxamide

HRID 1398492Notes

Reaction equation

HRID 1398492 reaction equation
[CH3:1][C:2]1([C:6]([OH:8])=O)[CH2:5][O:4][CH2:3]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:33][C:34]1[N:39]=[C:38]([N:40]2[C:48]3[C:43](=[CH:44][CH:45]=[C:46]([C:49]#[N:50])[CH:47]=3)[CH:42]=[N:41]2)[C:37]([NH2:51])=[CH:36][N:35]=1.C(N(CC)CC)C>CN(C=O)C.CCOC(C)=O>[NH2:33][C:34]1[N:39]=[C:38]([N:40]2[C:48]3[C:43](=[CH:44][CH:45]=[C:46]([C:49]#[N:50])[CH:47]=3)[CH:42]=[N:41]2)[C:37]([NH:51][C:6]([C:2]2([CH3:1])[CH2:5][O:4][CH2:3]2)=[O:8])=[CH:36][N:35]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 140289973-Methyl-3-oxetanecarboxylic AcidHCID 601639861-(2,5-Diaminopyrimidin-4-yl)indazole-6-carbonitrile

Product 1

HCID 60163988N-[2-amino-4-(6-cyano-1H-indazol-1-yl)pyrimidin-5-yl]-3-methyloxetane-3-carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 3-methyloxetane-3-carboxylic acid (17 mg, 0.143 mmol) and HATU (54.5 mg, 0.143 mmol) was added a solution of 1-(2,5-diaminopyrimidin-4-yl)-1H-indazole-6-carbonitrile (30 mg, 0.072 mmol) in DMF (0.5 mL) followed by triethylamine (0.030 mL, 0.215 mmol). The mixture was stirred at RT for 10 min, then diluted with EtOAc (10 mL) and washed with water (2×3 mL). The combined organic layer was dried over Na2SO4, filtered and concentrated in vacuo to give the crude compound. The crude product was purified by flash chromatography (Isolute column, 90% EtOAc in heptane to 100% EtOAc and then 0.5% MeOH/EtOAc) to afford the title compound as a pale yellow solid: 1H NMR (250 MHz, DMSO) δ 1.61 (3H, s), 4.31 (2H, d, J=5.94 Hz), 4.83 (2H, d, J=5.94 Hz), 7.20 (2H, br. s.), 7.65-7.92 (1H, m), 8.12 (1H, dd, J=8.22, 0.76 Hz), 8.49 (1H, s), 8.64 (1H, d, J=0.91 Hz), 9.14 (1H, s), 9.70 (1H, s); LC-MS: m/z=+350.1 (M+H)+.

Workup

  1. washwashed with water (2×3 mL)
  2. dry with materialThe combined organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give the crude compound
  6. customThe crude product was purified by flash chromatography (Isolute column, 90% EtOAc in heptane to 100% EtOAc

Sources & evidence

ORD record
ord-1bb3ce7af2174245b92deb584a55bb8d
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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