Water → Tert-butyl 6-((6-amino-5-(4-phenoxyphenyl)pyrimidin-4-yl)amino)-2-azaspiro[3.3]heptane-2-carboxylate

HRID 1522095Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]2([CH2:14][CH:13]([NH:15][C:16]3[C:21](Cl)=[C:20]([NH2:23])[N:19]=[CH:18][N:17]=3)[CH2:12]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O1CCOCC1.O.C(=O)([O-])[O-].[Cs+].[Cs+].[O:37]([C:44]1[CH:49]=[CH:48][C:47](B(O)O)=[CH:46][CH:45]=1)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:23][C:20]1[N:19]=[CH:18][N:17]=[C:16]([NH:15][CH:13]2[CH2:14][C:10]3([CH2:11][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9]3)[CH2:12]2)[C:21]=1[C:47]1[CH:48]=[CH:49][C:44]([O:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[CH:45][CH:46]=1

Participants

Conditions

Temperature: 140 °C

Procedure

In a microwave vial containing 6-(6-Amino-5-chloro-pyrimidin-4-ylamino)-2-aza-spiro[3.3]heptane-2-carboxylic acid tert-butyl ester (828.00 mg; 2.44 mmol; 1.00 eq.) in dioxane (4.00 ml; 46.94 mmol; 19.27 eq.) and water (0.40 ml; 22.20 mmol; 9.11 eq.) was added cesium carbonate (1190.86 mg; 3.65 mmol; 1.50 eq.), palladium(II) acetate (27.35 mg; 0.12 mmol; 0.05 eq.), 4-phenoxyphenylboronic acid (651.87 mg; 3.05 mmol; 1.25 eq.) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (100.03 mg; 0.24 mmol; 0.10 eq.). The reaction mixture was stirred at 140° C. for 16 h before it was concentrated and separated on a 50 g silica gel column with gradient EtOAc/Hexane (0-100%). The fractions were concentrated and carried to the next step.

Workup

concentrationwas concentrated
customseparated on a 50 g silica gel column with gradient EtOAc/Hexane (0-100%)
concentrationThe fractions were concentrated

Sources & evidence

ORD record: ord-c5caaf2d1773446aaf2abdb6c54b31db
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09073947B2

Reaction notes

Loading…