Triethylamine → HCID 54705117, compound

HRID 1664203Notes

Reaction equation

HRID 1664203 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]([C:12]2[N:13]=[C:14]3[C:20]4([CH2:25][CH2:24][O:23][CH2:22][CH2:21]4)[CH2:19][O:18][CH2:17][CH2:16][N:15]3[C:26](=[O:29])[C:27]=2[OH:28])=[O:11])=[C:4]([N:30]2[CH:34]=[N:33][C:32]([CH2:35][OH:36])=[N:31]2)[CH:3]=1.[CH2:37](N(CC)CC)C.S(Cl)(C)(=O)=O>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]([C:12]2[N:13]=[C:14]3[C:20]4([CH2:25][CH2:24][O:23][CH2:22][CH2:21]4)[CH2:19][O:18][CH2:17][CH2:16][N:15]3[C:26](=[O:29])[C:27]=2[OH:28])=[O:11])=[C:4]([N:30]2[CH:34]=[N:33][C:32]([CH2:35][O:36][CH3:37])=[N:31]2)[CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 54705132HCID 54705132, compound

Product 1

HCID 54705117HCID 54705117, compoundYield 103.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N-((4-fluoro-2-(3-(hydroxymethyl)-1H-1,2,4-triazol-1-yl)phenyl)methyl)-3′-hydroxy-4′-oxo-2,3,5,6,6′,7′-hexahydro-4′H-spiro[pyran-4,10′-pyrimido[1,2-d][1,4]oxazepine]-2′-carboxamide (190 mg, 0.32 mmol) was dissolved in 3 mL CH2Cl2 under N2 and treated with 100 mg triethylamine followed by mesylchloride (46 mg, 0.4 mmol) in 0.5 mL CH2Cl2. This was stirred for 30 min and then washed with dilute HCl. The crude product was purified by column chromatography on silica, eluted with EtOAc to give 170 mg of a clear gum. This was dissolved in 30 mL MeOH and heated at 70° C. in a sealed flask for 18 hrs and then concentrated. The residue was stirred with 5 mL TFA for 30 min and concentrated. The residue gave 45 mg of white crystals from 95%-EtOH. (Yield=34%) 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 3.50 (s, 3H) 3.55-4.13 (m, 14H) 4.50 (d, J=5.80 Hz, 2H) 4.63 (s, 2H) 7.06-7.28 (m, 2H) 7.69 (dd, J=8.55, 5.80 Hz, 1H) 8.36 (t, J=6.87 Hz, 1H) 8.40 (s, 1H) 12.10 (s, 1H); HRMS (M+H) calcd for C24H27FN6O6: 515.2054; found: 515.2032.

Workup

  1. washwashed with dilute HCl
  2. customThe crude product was purified by column chromatography on silica
  3. washeluted with EtOAc

Sources & evidence

ORD record
ord-fc04bb8e316f453c8328f65fa749e4c9
Source dataset
uspto-grants-2011_10
Patent number
US08039458B2

Reaction notes

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