Diisopropylethylamine → HCID 86762234, compound

HRID 1619047Notes

Reaction equation

HRID 1619047 reaction equation
[F:1][C:2]1[S:6][C:5]([C@:7]23[CH2:15][NH:14][CH2:13][C@H:12]2[CH2:11][S:10][C:9]([NH:16][C:17](=[O:24])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[N:8]3)=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.Cl[C:35]1[N:40]=[CH:39][C:38]([F:41])=[CH:37][N:36]=1>O1CCOCC1.C(OCC)(=O)C>[F:41][C:38]1[CH:37]=[N:36][C:35]([N:14]2[CH2:13][C@@H:12]3[C@@:7]([C:5]4[S:6][C:2]([F:1])=[CH:3][CH:4]=4)([N:8]=[C:9]([NH:16][C:17](=[O:24])[C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[S:10][CH2:11]3)[CH2:15]2)=[N:40][CH:39]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 5834662-Chloro-5-fluoropyrimidineHCID 86762235HCID 86762235, compound

Product 1

HCID 86762234HCID 86762234, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a stirred mixture of the N-[(4aR,7aR)-7a-(5-fluorothiophen-2-yl)-4,4a,5,6,7,7a-hexahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (415 mg, 1.15 mmol) in 1,4-dioxane (23 mL) is added diisopropylethylamine (601 μL, 3.44 mmol) and 2-chloro-5-fluoropyrimidine (1.10 mL, 11.5 mmol). The solution is heated to reflux for 3 hours. The pale yellow solution is allowed to cool, diluted with ethyl acetate, (120 mL) and washed with dilute aqueous sodium bicarbonate (100 mL, prepared from 50 mL saturated sodium bicarbonate and 50 mL water), water (50 mL), and brine (50 mL). The organic phase is dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica gel chromatography eluting with hexanes/ethyl acetate, gradient from 60:40 to 30:70, to give the title compound (435 mg, 83%) as a white foam. ES/MS (m/e): 458.0 (M+H).

Workup

  1. temperatureThe solution is heated
  2. temperatureto reflux for 3 hours
  3. temperatureto cool
  4. washwashed with dilute aqueous sodium bicarbonate (100 mL, prepared from 50 mL saturated sodium bicarbonate and 50 mL water), water (50 mL), and brine (50 mL)
  5. dry with materialThe organic phase is dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is purified by silica gel chromatography
  9. washeluting with hexanes/ethyl acetate, gradient from 60:40 to 30:70

Sources & evidence

ORD record
ord-f87b7aede5534c8da1ca62c91cbf0372
Source dataset
uspto-grants-2014_07
Patent number
US08772282B2

Reaction notes

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