Sodium t-butoxide → 4-chloro-7-(4-methoxybenzyl)-N-(8-morpholino-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-amine

HRID 1487239Notes

Reaction equation

HRID 1487239 reaction equation
Cl[C:2]1[N:3]=[C:4]([Cl:20])[C:5]2[CH2:10][CH2:9][N:8]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[C:6]=2[N:7]=1.[O:21]1[CH2:26][CH2:25][N:24]([C:27]2[C:32]3[O:33][CH2:34][CH2:35][O:36][C:31]=3[C:30]([NH2:37])=[CH:29][CH:28]=2)[CH2:23][CH2:22]1.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:20][C:4]1[C:5]2[CH2:10][CH2:9][N:8]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[C:6]=2[N:7]=[C:2]([NH:37][C:30]2[C:31]3[O:36][CH2:35][CH2:34][O:33][C:32]=3[C:27]([N:24]3[CH2:25][CH2:26][O:21][CH2:22][CH2:23]3)=[CH:28][CH:29]=2)[N:3]=1

Participants

5

Reactant 3

HCID 23676156Sodium t-butoxideHCID 682847868-Morpholino-2,3-dihydrobenzo[b][1,4]dioxin-5-amine2×HCID 866996702,4-dichloro-7-(4-methoxybenzyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine2×

Product 1

HCID 866996914-chloro-7-(4-methoxybenzyl)-N-(8-morpholino-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-amineYield 61%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

According to General Protocol II, 4-chloro-7-(4-methoxybenzyl)-N-(8-morpholino-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-6,7-dihydro-5H-pyrrolo[2,3-c]pyrimidin-2-amine was prepared from 2,4-dichloro-7-(4-methoxybenzyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine (Intermediate A1, 200 mg, 0.645 mmol), 8-morpholino-2,3-dihydrobenzo[b][1,4]dioxin-5-amine (Intermediate B4, 152 mg, 0.644 mmol), Pd2(dba)3 (118 mg, 0.129 mmol), (±)-BINAP (80 mg, 0.129 mmol) and sodium tert-butoxide (124 mg, 1.292 mmol) in a microwave tube at 100° C. for 10 minutes, and isolated as a yellow solid (200 mg, yield 61%). 1H NMR (400 MHz, CDCl3) δ ppm 8.01-8.03 (d, 1H, J=8.8 Hz), 7.21-7.24 (d, 2H, J=8.4 Hz), 6.86-6.88 (d, 2H, J=8.8 Hz), 6.51-6.54 (d, 1H, J=8.8 Hz), 4.54 (s, 2H), 4.30-4.34 (m, 4H), 3.86-3.89 (m, 4H), 3.80 (s, 3H), 3.46-3.50 (m, 2H), 3.00-3.03 (m, 4H), 2.91-2.95 (m, 2H).

Sources & evidence

ORD record
ord-db7d2ed5db7e46acaab49c0c65d9d329
Source dataset
uspto-grants-2016_08
Patent number
US09428508B2

Reaction notes

Loading…