Glycolic Acid → HCID 58529519, compound

HRID 1972826Notes

Reaction equation

HRID 1972826 reaction equation
[CH2:1]([N:8]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:17]3[CH:18]=[C:19]([CH:27]4[O:32][CH2:31][CH:30]5[CH2:33][NH:34][CH2:35][CH2:36][N:29]5[CH2:28]4)[N:20]4[C:25]=3[C:24]([NH2:26])=[N:23][CH:22]=[N:21]4)[CH:13]=[CH:14]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:44](O)(=[O:47])[CH2:45][OH:46].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[NH2:26][C:24]1[C:25]2=[C:17]([C:12]3[CH:13]=[CH:14][C:15]4[C:10]([CH:11]=3)=[N:9][N:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:16]=4)[CH:18]=[C:19]([CH:27]3[O:32][CH2:31][CH:30]4[CH2:33][N:34]([C:45](=[O:46])[CH2:44][OH:47])[CH2:35][CH2:36][N:29]4[CH2:28]3)[N:20]2[N:21]=[CH:22][N:23]=1

Participants

6

Reactant 4

HCID 757Glycolic AcidHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 58529380HCID 58529380, compound

Product 1

HCID 58529519HCID 58529519, compoundYield 37.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 5-(2-benzyl-2H-indazol-6-yl)-7-(octahydropyrazino[2,1-c][1,4]oxazin-3-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (50 mg, 0.10 mmol), triethylamine (43 μL, 0.31 mmol), and glycolic acid (8 mg, 0.10 mmol) in DMF (1 mL), benzotriazol-1-yloxytris(dimethylamino)-phosphonium hexafluorophosphate (51 mg, 0.11 mmol) was added at 0° C. The reaction was allowed to stir for 30 minutes while warming to rt. The mixture was partitioned between ethyl acetate (30 mL) and saturated aqueous K2CO3 solution (10 mL). The layers were separated and the organic phase was washed, dried (Na2SO4), and concentrated to dryness. The residue was triturated with Et2O to obtain 20 mg (36%) of the desired product. 1H-NMR (DMSO-d6) 8.53 (s, 1H), 7.91 (s, 1H), 7.78 (d, 1H), 7.57 (s, 1H), 7.35 to 7.27 (m, 5H), 7.11 (dd, 1H), 6.71 (s, 1H), 5.64 (s, 2H), 5.16-5.12 (m, 1H), 4.35-3.96 (m, 3H), 3.88-3.85 (m, 1H), 3.67-3.55 (m, 1H), 3.36-3.27 (m, 1H), 3.12-3.01 (m, 1H), 2.79-2.64 (m, 2H), 2.55-2.41 (m, 3H), 2.19-2.10 (m, 2H); LC-MS [M+H]+=539, RT=2.19 min.

Workup

  1. customThe mixture was partitioned between ethyl acetate (30 mL) and saturated aqueous K2CO3 solution (10 mL)
  2. customThe layers were separated
  3. washthe organic phase was washed
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated to dryness
  6. customThe residue was triturated with Et2O

Sources & evidence

ORD record
ord-bc50d41421b048d7a3818850a4fa7b2a
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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