Triphosgene → HCID 123350859, compound

HRID 920765Notes

Reaction equation

HRID 920765 reaction equation
[CH2:1]([O:8][CH:9]1[CH2:12][C:11]([CH3:14])([NH2:13])[CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:16](Cl)([O:18]C(=O)OC(Cl)(Cl)Cl)Cl.[Cl:27][C:28]1[CH:29]=[C:30]([C:35]2[C:43]([C:44]([NH2:46])=[O:45])=[C:38]3[CH2:39][NH:40][CH2:41][CH2:42][N:37]3[N:36]=2)[CH:31]=[CH:32][C:33]=1[F:34]>C1COCC1>[CH2:1]([O:8][CH:9]1[CH2:12][C:11]([NH:13][C:16]([N:40]2[CH2:41][CH2:42][N:37]3[N:36]=[C:35]([C:30]4[CH:31]=[CH:32][C:33]([F:34])=[C:28]([Cl:27])[CH:29]=4)[C:43]([C:44]([NH2:46])=[O:45])=[C:38]3[CH2:39]2)=[O:18])([CH3:14])[CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 94429TriphosgeneHCID 1180616272-(3-Chloro-4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-carboxamideHCID 118062791HCID 118062791, compound

Product 1

HCID 123350859HCID 123350859, compoundYield 40.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 3-(benzyloxy)-1-methylcyclobutanamine (64.9 mg, 0.339 mmol) in THF (10 mL) was added TEA (0.14 mL, 1.357 mmol) followed by triphosgene (100 mg, 0.339 mmol) at 0° C. After stirring for 10 min, a solution of Intermediate 185B (100 mg, 0.34 mmol) in THF (2 mL) was added at 0° C. and the resulting solution was allowed to warm to RT and stir for 16 h. The reaction mixture was quenched with a saturated aqueous solution of NH4Cl and extracted with DCM (3×20 mL). The combined organic layers were dried over Na2SO4 and evaporated to afford the crude reaction mixture which was purified by silica gel chromatography (12 g REDISEP® column, eluting with 2% MeOH in CHCl3). Fractions containing the product were combined and evaporated to afford Intermediate 260A (70 mg, 40% yield) as a pale yellow solid. MS(ES): m/z=512 [M+H]+.

Workup

  1. stirringstir for 16 h
  2. customThe reaction mixture was quenched with a saturated aqueous solution of NH4Cl
  3. extractionextracted with DCM (3×20 mL)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. customevaporated
  6. customto afford the crude
  7. customreaction mixture which
  8. customwas purified by silica gel chromatography (12 g REDISEP® column, eluting with 2% MeOH in CHCl3)
  9. additionFractions containing the product
  10. customevaporated

Sources & evidence

ORD record
ord-145d43bb067f463c9e94323de0a5a1f3
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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