Triethylamine → 1-{[1-(2-aminopyrimidin-4-yl)-6-iodo-1H-indazol-3-yl]carbonyl}azetidin-3-ol

HRID 1398587

Reaction equation

HRID 1398587 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:17])[CH:15]=3)[C:10]([C:18]([OH:20])=O)=[N:9]2)[CH:5]=[CH:4][N:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH:46]1[CH2:49][CH:48]([OH:50])[CH2:47]1.C(N(CC)CC)C>CN(C=O)C.CCOC(C)=O.O>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([I:17])[CH:15]=3)[C:10]([C:18]([N:46]3[CH2:49][CH:48]([OH:50])[CH2:47]3)=[O:20])=[N:9]2)[CH:5]=[CH:4][N:3]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 27592903-Hydroxyazetidine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 681816001-(2-Aminopyrimidin-4-yl)-6-iodoindazole-3-carboxylic acid

Product 1

HCID 681818701-{[1-(2-aminopyrimidin-4-yl)-6-iodo-1H-indazol-3-yl]carbonyl}azetidin-3-ol

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-(2-amino-pyrimidin-4-yl)-6-iodo-1H-indazole-3-carboxylic acid (500 mg, 1.08 mmol) in DMF (5 ml) was added HATU (823.46 mg, 2.17 mmol) followed by azetidin-3-ol HCl (237.26 mg, 2.17 mmol) and triethylamine (0.45 ml, 3.25 mmol). The reaction mixture was stirred at RT for 3 hr. A white precipitate was also observed which was not soluble in EtOAc and water. The solid was filtered and washed with EtOAc and the filtrate worked up. The solid was dried and analysed by LCMS found to be clean title compound. To the filtrate water (6 ml) was added and the product extracted into EtOAc (2×10 ml). The combined organics were washed with water and brine and concentrated in vacuo. The material was then purified by column chromatography, (9:1 DCM: methanol). The combined column fractions were then triturated from acetonitrile to give the title compound; 1H NMR (500 MHz, DMSO) 3.86 (1H, dd, J=10.56, 3.94 Hz), 4.26-4.46 (2H, m), 4.52-4.64 (1H, m), 4.88 (1H, dd, J=9.77, 7.25 Hz), 5.83 (1H, d, J=6.62 Hz), 7.10 (1H, d, J=5.36 Hz), 7.17 (2H, br. s), 7.77 (1H, d, J=8.51 Hz), 8.04 (1H, d, J=8.51 Hz), 8.36 (1H, d, J=5.67 Hz), 9.34 (1 H, s). LC-MS: m/z=+436.95 (M+H)+.

Workup

  1. filtrationThe solid was filtered
  2. washwashed with EtOAc
  3. customThe solid was dried
  4. additionTo the filtrate water (6 ml) was added
  5. extractionthe product extracted into EtOAc (2×10 ml)
  6. washThe combined organics were washed with water and brine
  7. concentrationconcentrated in vacuo
  8. customThe material was then purified by column chromatography, (9:1 DCM: methanol)
  9. customThe combined column fractions were then triturated from acetonitrile

Sources & evidence

ORD record
ord-df98b44d8e384e8b974e203ca0fbc2ea
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Linked notes

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