Di-tert-butyl dicarbonate → 6-(4-(4-amino-3-hydroxyazepan-1-yl)furo[3,2-d]pyrimidin-2-ylamino)-2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-one

HRID 1038819Notes

Reaction equation

HRID 1038819 reaction equation
[NH2:1][CH:2]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]2[C:10]3[O:31][CH:30]=[CH:29][C:11]=3[N:12]=[C:13]([NH:15][C:16]3[CH:28]=[CH:27][C:19]4[O:20][C:21]([CH3:26])([CH3:25])[C:22](=[O:24])[NH:23][C:18]=4[CH:17]=3)[N:14]=2)[CH2:4][CH:3]1[O:32][Si](C(C)(C)C)(C)C.CC(OC(OC(OC(C)(C)C)=O)=O)(C)C.ClC1N=C(Cl)C2OC=CC=2N=1.NC1C=CC2OC(C)(C)C(=O)NC=2C=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[NH2:1][CH:2]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]2[C:10]3[O:31][CH:30]=[CH:29][C:11]=3[N:12]=[C:13]([NH:15][C:16]3[CH:28]=[CH:27][C:19]4[O:20][C:21]([CH3:26])([CH3:25])[C:22](=[O:24])[NH:23][C:18]=4[CH:17]=3)[N:14]=2)[CH2:4][CH:3]1[OH:32]

Participants

7

Reactant 5

HCID 90495Di-tert-butyl dicarbonateHCID 2724141Tetrabutylammonium FluorideHCID 136654966-Amino-2,2-dimethyl-2H-benzo[B][1,4]oxazin-3(4H)-oneHCID 457899682,4-Dichlorofuro[3,2-D]pyrimidineHCID 687516286-(4-(4-amino-3-(tert-butyldimethylsilyloxy)azepan-1-yl)furo[3,2-d]pyrimidin-2-ylamino)-2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-one

Product 1

HCID 687531326-(4-(4-amino-3-hydroxyazepan-1-yl)furo[3,2-d]pyrimidin-2-ylamino)-2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-oneYield 35%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 6-(4-(4-amino-3-(tert-butyldimethylsilyloxy)azepan-1-yl)furo[3,2-d]pyrimidin-2-ylamino)-2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-one (0.400 g, 0.724 mmol, prepared using F from Preparation #AH.1, O with Boc2O, K, A with 2,4-dichlorofuro[3,2-d]pyrimidine [Arkpharm], B with 6-amino-2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-one [ArkPharm] and C) and TBAF (0.378 g, 1.45 mmol) in THF (10 mL) was stirred at about 25° C. for about 4 h. The mixture was concentrated and purified by preparatory HPLC (Table 2, Method t) to give 6-(4-(4-amino-3-hydroxyazepan-1-yl)furo[3,2-d]pyrimidin-2-ylamino)-2,2-dimethyl-2H-benzo[b][1,4]oxazin-3(4H)-one (0.11 g, 35%): LC/MS (Table 2, Method h) Rt=1.69 min.; MS m/z: 439 (M+H)+. Syk IC50=B

Workup

  1. customprepared
  2. concentrationThe mixture was concentrated
  3. custompurified by preparatory HPLC (Table 2, Method t)

Sources & evidence

ORD record
ord-6eccb6f64d1f42baa9446daee92b1078
Source dataset
uspto-grants-2013_10
Patent number
US08551981B2

Reaction notes

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