1,2,3,4-Tetrahydroisoquinoline → 4-(3,4-dihydro-1H-isoquinolin-2-yl)-6-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrido[3,2-d]pyrimidine

HRID 1469097Notes

Reaction equation

[NH:1]1[C:5]2=[N:6][CH:7]=[C:8]([C:10]3[CH:11]=[CH:12][C:13]4[N:14]=[CH:15][NH:16][C:17](=O)[C:18]=4[N:19]=3)[CH:9]=[C:4]2[CH:3]=[CH:2]1.[CH2:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:24][CH2:23][NH:22]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.N12CCCN=C1CCCCC2>C(#N)C.CN(C)C=O>[CH2:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:24][CH2:23][N:22]1[C:17]1[C:18]2[N:19]=[C:10]([C:8]3[CH:9]=[C:4]4[CH:3]=[CH:2][NH:1][C:5]4=[N:6][CH:7]=3)[CH:11]=[CH:12][C:13]=2[N:14]=[CH:15][N:16]=1

Participants

Conditions

Temperature: 60 °C

Procedure

0.20 g of 6-(1H-pyrrolo[2,3-b]pyridin-5-yl)-3H-pyrido[3,2-d]pyrimidin-4-one and 139 μl of 1,2,3,4-tetrahydroisoquinoline are suspended in 10 ml of acetonitrile and 1 ml of dimethylformamide in a flask. 0.65 g of (benzotriazol-1-yloxy)tris-(dimethylamino)phosphonium hexafluorophosphate, 255 μl of 1,8-diaza-bicyclo[5.4.0]undec-7-ene are subsequently added, and the mixture is heated at 60° C. under nitrogen until the reaction has proceeded to completion (HPLC check, about 5 hours). A precipitate precipitates out of the reaction solution. This is filtered off, rinsed with water and dried, giving 0.20 g of 4-(3,4-dihydro-1H-isoquinolin-2-yl)-6-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrido[3,2-d]pyrimidine (“A6”) as white solid (yield 65%, content 94%); MS-FAB (M+H+)=379.1; Rf (polar method): 1.86 min;

Workup

customhas proceeded to completion (HPLC check, about 5 hours)
customA precipitate precipitates out of the reaction solution
filtrationThis is filtered off
washrinsed with water
customdried

Sources & evidence

ORD record: ord-971c5dceb3f14639917ef45ed3ccf3fc
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09006255B2

Reaction notes

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