Triethylamine → 4-[1-(2-aminopyrimidin-4-yl)-3-({2-oxa-6-azaspiro[3.3]heptan-6-yl}carbonyl)-1H-indazol-6-yl]-2-(pyrimidin-2-yl)but-3-yn-2-ol

HRID 1398592Notes

Reaction equation

HRID 1398592 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]([C:17]#[C:18][C:19]([OH:27])([C:21]4[N:26]=[CH:25][CH:24]=[CH:23][N:22]=4)[CH3:20])[CH:15]=3)[C:10]([C:28]([OH:30])=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.C(O)(=O)C(O)=O.[CH2:61]1[C:64]2([CH2:67][NH:66][CH2:65]2)[CH2:63][O:62]1.C(N(CC)CC)C>CN(C=O)C.O>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]#[C:18][C:19]([C:21]4[N:26]=[CH:25][CH:24]=[CH:23][N:22]=4)([OH:27])[CH3:20])[CH:15]=3)[C:10]([C:28]([N:66]3[CH2:67][C:64]4([CH2:61][O:62][CH2:63]4)[CH2:65]3)=[O:30])=[N:9]2)[CH:5]=[CH:4][N:3]=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 53308464Oxalic acid--2-oxa-6-azaspiro(3.3)heptane (1/1)HCID 681816771-(2-Aminopyrimidin-4-yl)-6-[3-hydroxy-3-(pyrimidin-2-yl)but-1-yn-1-yl]indazole-3-carboxylic acid

Product 1

HCID 681817784-[1-(2-aminopyrimidin-4-yl)-3-({2-oxa-6-azaspiro[3.3]heptan-6-yl}carbonyl)-1H-indazol-6-yl]-2-(pyrimidin-2-yl)but-3-yn-2-ol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(2-aminopyrimidin-4-yl)-6-[3-hydroxy-3-(pyrimidin-2-yl)but-1-yn-1-yl]indazole-3-carboxylic acid (100 mg, 0.25 mmol) in DMF (2 ml) was added HATU (189.46 mg, 0.5 mmol) followed by 2-oxa-6-azaspiro[3.3]heptane oxalate (94.26 mg, 0.5 mmol) and triethylamine (0.1 ml, 0.75 mmol). The reaction mixture was stirred at RT for 16 hr. Water (2 ml) was added to the reaction mixture and the product extracted into EtOAc (2×5 ml). The combined organics were washed with water (3 mL) and brine (3 mL) and concentrated in vacuo. The crude product was purified twice by flash chromatography (Biotage, 2-12% methanol in DCM) to give the title compound: 1H NMR (500 MHz, DMSO) delta 1.93 (3H, s), 4.31 (2H, s), 4.74 (4H, q, J=6.9 Hz), 4.87 (2H, s), 6.26 (1H, s), 7.02-7.32 (3H, m), 7.41 (1H, dd, J=8.4, 1.2 Hz), 7.51 (1H, t, J=4.9 Hz), 8.23 (1H, d, J=8.0 Hz), 8.39 (1H, d, J=5.5 Hz), 8.75-9.10 (3H, m); LC-MS: m/z=+483.10 (M+H)+.

Workup

  1. extractionthe product extracted into EtOAc (2×5 ml)
  2. washThe combined organics were washed with water (3 mL) and brine (3 mL)
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified twice by flash chromatography (Biotage, 2-12% methanol in DCM)

Sources & evidence

ORD record
ord-3b7d97e718f0467c985e9f1207a67ed6
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

Loading…