Hydrochloric Acid → N4-(3-aminophenyl)-N2-(1,4-benzoxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine

HRID 1483510Notes

Reaction equation

HRID 1483510 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([NH:10][C:11]2[C:16]([F:17])=[CH:15][N:14]=[C:13]([NH:18][C:19]3[CH:20]=[CH:21][C:22]4[O:27][CH2:26][C:25](=O)[NH:24][C:23]=4[CH:29]=3)[N:12]=2)[CH:7]=[CH:8][CH:9]=1)([O-])=O.Cl>CCO.[Pd]>[NH2:1][C:4]1[CH:5]=[C:6]([NH:10][C:11]2[C:16]([F:17])=[CH:15][N:14]=[C:13]([NH:18][C:19]3[CH:20]=[CH:21][C:22]4[O:27][CH2:26][CH:25]=[N:24][C:23]=4[CH:29]=3)[N:12]=2)[CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 66759406HCID 66759406, compound

Product 1

HCID 66759504N4-(3-aminophenyl)-N2-(1,4-benzoxazin-6-yl)-5-fluoro-2,4-pyrimidinediamineYield 21.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

N4-(3-Nitrophenyl)-N2-[(2H) 1,4-benzoxazin-3(4H)-one-6-yl]-5-fluoro-2,4-pyrimidinediamine (940 mg, 2.5 mmol) and Pd/C 10% (300 mg, 50% water content) were suspended in EtOH (7 mL) and 10% aqueous HCl (5 mL) and hydrogenated in a Parr apparatus for 3 hours (22° C., 60 psi). The suspension was filtered over celite and neutralized by addition of K2CO3. The solvents were removed and the resulting black slurry was suspended in MeOH. Silica gel (4 g) was added and the volatiles were removed under reduced pressure. The residue was subjected to column chromatography on silica gel (CHCl3-Acetone, 2:1) to give 186 mg of N4-(3-aminophenyl)-N2-(1,4-benzoxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine as brownish solid. 1H NMR (DMSO-d6): δ 8.92 (s, 1H), 8.64 (s, 1H), 7.95 (d, 1H, J=3.6 Hz), 7.11 (s, 1H), 6.84-6.95 (m, 3H), 6.66 (dd, 1H, J=2.4, 9.0 Hz), 6.46 (d, 1H, J=8.1 Hz), 6.28 (d, 1H, J=8.1 Hz), 5.62 (s, 1H), 4.98 (s, 2H), 4.03 (m, 2H), 3.31 (m, 2H); LCMS purity: 98.4%; MS (m/e): 352.7 (M+, 100).

Workup

  1. filtrationThe suspension was filtered over celite
  2. additionneutralized by addition of K2CO3
  3. customThe solvents were removed
  4. additionSilica gel (4 g) was added
  5. customthe volatiles were removed under reduced pressure

Sources & evidence

ORD record
ord-af0148bf5ebf44e5871caa5c526c5ae7
Source dataset
uspto-grants-2016_08
Patent number
US09416112B2

Reaction notes

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