4-Aminopyrimidine → HCID 89761876, compound

HRID 528634Notes

Reaction equation

HRID 528634 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][O:11][C:10]3[CH:14]=[C:15]([S:18]([O:21]C4C(F)=C(F)C(F)=C(F)C=4F)(=O)=[O:19])[CH:16]=[CH:17][C:9]2=3)=[C:4]([C:33]#[N:34])[CH:3]=1.[NH2:35][C:36]1[CH:41]=[CH:40][N:39]=[CH:38][N:37]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][O:11][C:10]3[CH:14]=[C:15]([S:18]([NH:35][C:36]4[CH:41]=[CH:40][N:39]=[CH:38][N:37]=4)(=[O:19])=[O:21])[CH:16]=[CH:17][C:9]2=3)=[C:4]([C:33]#[N:34])[CH:3]=1

Participants

5

Reactant 3

HCID 689584-AminopyrimidineHCID 2733832Lithium HexamethyldisilazideHCID 89761782HCID 89761782, compound

Product 1

HCID 89761876HCID 89761876, compoundYield 15.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of perfluorophenyl 4-(4-chloro-2-cyanophenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonate (370 mg, 0.717 mmol) and 4-amino pyrimidine (102 mg, 1.07 mmol) in THF (5 mL) was added LiHMDS (1M in THF, 1.43 mL, 1.43 mmol) at −78° C. The reaction mixture was stirred at −78° C. for 5 min and at 0° C. for 1 h. After completion, the reaction mixture was quenched with 2-3 drops of acetic acid and concentrated under reduced pressure. The crude mass was purified by combi flash column chromatography (12 g column; elution: 2.5% methanol in DCM) to provide 4-(4-chloro-2-cyanophenyl)-N-(pyrimidin-4-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (48 mg, 15.6%) as an off-white solid. 1H NMR (400 MHz, DMSO) δ 11.87 (s, 1H), 8.66 (s, 1H), 8.40 (s, 1H) 8.15 (d, J=2.4 Hz, 1H), 7.86 (dd, J=8.7, 2.5 Hz, 1H), 7.60 (d, J=8.8 Hz, 1H), 7.12-6.96 (m, 1H), 7.43-7.24 (m, 2H), 6.56 (d, J=8.6 Hz, 1H), 4.34 (s, 2H), 3.77 (s, 2H); LCMS (ESI) m/z; 427.95 (M+H).

Workup

  1. customAfter completion, the reaction mixture was quenched with 2-3 drops of acetic acid
  2. concentrationconcentrated under reduced pressure
  3. customThe crude mass was purified by combi flash column chromatography (12 g column; elution: 2.5% methanol in DCM)

Sources & evidence

ORD record
ord-9ba892709f46448ab0625ec6d040cc38
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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