Phosphorus oxychloride → 8-(3,3,4,4,4-Pentafluorobutyl)imidazo[1,5-a]pyrimidine-6-carbonitrile

HRID 2203390Notes

Reaction equation

HRID 2203390 reaction equation
[F:1][C:2]([F:21])([C:17]([F:20])([F:19])[F:18])[CH2:3][CH2:4][C:5]1[N:6]=[C:7]([C:14]([NH2:16])=O)[N:8]2[CH:13]=[CH:12][CH:11]=[N:10][C:9]=12.P(Cl)(Cl)(Cl)=O>>[F:21][C:2]([F:1])([C:17]([F:19])([F:18])[F:20])[CH2:3][CH2:4][C:5]1[N:6]=[C:7]([C:14]#[N:16])[N:8]2[CH:13]=[CH:12][CH:11]=[N:10][C:9]=12

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 76849900Imidazo[1,5-a]pyrimidine-6-carboxamide,8-(3,3,4,4,4-pentafluorobutyl)-

Product 1

HCID 866790298-(3,3,4,4,4-Pentafluorobutyl)imidazo[1,5-a]pyrimidine-6-carbonitrile

Procedure

A solution of the intermediate from Step E in phosphoryl chloride (9.43 mL, 101 mmol) was heated at 105° C. for 30 min. The majority of the phosphoryl chloride was removed in vacuo. The crude product was partitioned between saturated aq. NaHCO3 and EtOAc. The aqueous layer was separated and further extracted with EtOAc (2×). The combined extracts were dried (Na2SO4) and concentrated in vacuo to give the desired product, as a yellow solid. 1H NMR (600 MHz, CHCl3-d) δ 8.47 (dd, J=7.1, 1.6 Hz, 1H); 8.41 (dd, J=3.8, 1.7 Hz, 1H); 6.98 (dd, J=7.1, 3.8 Hz, 1H); 3.35-3.31 (m, 2H); 2.68-2.57 (m, 2H). m/z=291.1 (M+H).

Workup

  1. customThe majority of the phosphoryl chloride was removed in vacuo
  2. customThe crude product was partitioned between saturated aq. NaHCO3 and EtOAc
  3. customThe aqueous layer was separated
  4. extractionfurther extracted with EtOAc (2×)
  5. dry with materialThe combined extracts were dried (Na2SO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d6130f09cdd84d95a0571424fc8f1a55
Source dataset
uspto-grants-2016_06
Patent number
US09365574B2

Reaction notes

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