Triphenylphosphine → 6-(4-(4-(aminomethyl)-4-methoxypiperidin-1-yl)furo[3,2-d]pyrimidin-2-ylamino)-2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-one

HRID 1038810Notes

Reaction equation

HRID 1038810 reaction equation
[N:1]([CH2:4][C:5]1([O:34][CH3:35])[CH2:10][CH2:9][N:8]([C:11]2[C:12]3[O:33][CH:32]=[CH:31][C:13]=3[N:14]=[C:15]([NH:17][C:18]3[CH:30]=[CH:29][C:21]4[O:22][C:23]([CH3:28])([CH3:27])[C:24](=[O:26])[NH:25][C:20]=4[CH:19]=3)[N:16]=2)[CH2:7][CH2:6]1)=[N+]=[N-].N(CC1(OC)CCN(C(OC(C)(C)C)=O)CC1)=[N+]=[N-].ClC1N=C(Cl)C2OC=CC=2N=1.NC1C=CC2OC(C)(C)C(=O)NC=2C=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.O>[NH2:1][CH2:4][C:5]1([O:34][CH3:35])[CH2:6][CH2:7][N:8]([C:11]2[C:12]3[O:33][CH:32]=[CH:31][C:13]=3[N:14]=[C:15]([NH:17][C:18]3[CH:30]=[CH:29][C:21]4[O:22][C:23]([CH3:27])([CH3:28])[C:24](=[O:26])[NH:25][C:20]=4[CH:19]=3)[N:16]=2)[CH2:9][CH2:10]1

Participants

8

Reactant 5

HCID 11776TriphenylphosphineHCID 136654966-Amino-2,2-dimethyl-2H-benzo[B][1,4]oxazin-3(4H)-oneHCID 457899682,4-Dichlorofuro[3,2-D]pyrimidineHCID 58504149Tert-butyl 4-(azidomethyl)-4-methoxypiperidine-1-carboxylateHCID 866650986-(4-(4-(azidomethyl)-4-methoxypiperidin-1-yl)furo[3,2-d]pyrimidin-2-ylamino)-2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-one

Product 1

HCID 687506336-(4-(4-(aminomethyl)-4-methoxypiperidin-1-yl)furo[3,2-d]pyrimidin-2-ylamino)-2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-oneYield 76%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 6-(4-(4-(azidomethyl)-4-methoxypiperidin-1-yl)furo[3,2-d]pyrimidin-2-ylamino)-2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-one (0.030 g, 0.063 mmol, prepared using C from tert-butyl 4-(azidomethyl)-4-methoxypiperidine-1-carboxylate [WO 2010/080864, Example 257], A with 2,4-dichlorofuro[3,2-d]pyrimidine [ArkPharm] and B with 6-amino-2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-one [ArkPharm]) and triphenylphosphine (0.025 g, 0.094 mmol) in THF (16 mL) and water (2 mL) was stirred at about 100° C. overnight. The organic phase was removed and diluted with water. The aqueous phase was neutralized with aqueous 2 N NaOH and extracted with EtOAc. The combined organic phase was washed with brine and dried over Na2SO4, filtered, concentrated under vacuum and purified by HPLC (Table 2, Method v) to afford 6-(4-(4-(aminomethyl)-4-methoxypiperidin-1-yl)furo[3,2-d]pyrimidin-2-ylamino)-2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-one (0.022 g, 76%). LC/MS (Table 2, method h) Rt=1.77 min.; MS m/z: 453 (M+H)+. Syk IC50=A

Workup

  1. customprepared
  2. customThe organic phase was removed
  3. additiondiluted with water
  4. extractionextracted with EtOAc
  5. washThe combined organic phase was washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. custompurified by HPLC (Table 2, Method v)

Sources & evidence

ORD record
ord-85d6e2b468ea4ef6ad395896e46bcecf
Source dataset
uspto-grants-2013_10
Patent number
US08551981B2

Reaction notes

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