Cesium carbonate → (+/-)-2-((2-chloro-5-cyano-3-((4aR,8aR)-hexahydro-1H-pyrido[3,4-b][1,4]oxazin-6(7H)-yl)phenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 1430910Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([N:8]([CH2:18][CH3:19])CC2C=CC(OC)=CC=2)[C:5]2=[N:20][CH:21]=[C:22]([C:23]#[N:24])[N:4]2[N:3]=1.[NH2:25][C:26]1[C:27]([Cl:51])=[C:28]([N:34]2[CH2:43][CH2:42][C@@H:41]3[C@H:36]([O:37][CH2:38][CH2:39][N:40]3C(OC(C)(C)C)=O)[CH2:35]2)[CH:29]=[C:30]([C:32]#[N:33])[CH:31]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[Cl:51][C:27]1[C:28]([N:34]2[CH2:43][CH2:42][C@@H:41]3[C@H:36]([O:37][CH2:38][CH2:39][NH:40]3)[CH2:35]2)=[CH:29][C:30]([C:32]#[N:33])=[CH:31][C:26]=1[NH:25][C:2]1[N:7]=[C:6]([NH:8][CH2:18][CH3:19])[C:5]2=[N:20][CH:21]=[C:22]([C:23]#[N:24])[N:4]2[N:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

2-chloro-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Intermediate 10) (85.0 mg, 0.248 mmol), (+/−)-(4aR,8aR)-tert-butyl 6-(3-amino-2-chloro-5-cyanophenyl)octahydro-1H-pyrido[3,4-b][1,4]oxazine-1-carboxylate (97.0 mg, 0.248 mmol), DPPF (9.62 mg, 0.017 mmol), Cs2CO3 (137 mg, 0.422 mmol), Xantphos (14.35 mg, 0.025 mmol), Palladium(II)Acetate (16.7 mg, 0.074 mmol) and 1,4-dioxane (2 ml) were combined in a microwave vial. The vial was evacuated and backfilled with Nitrogen (3×). The reaction stirred at 100° C. for 3 hr.

Workup

customThe vial was evacuated

Sources & evidence

ORD record: ord-a22751b620a14776b59230957181e6b9
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940736B2

Reaction notes

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