Carbon Tetrachloride → 4-(6-Chloro-2,3-dihydro-indol-1-yl)-6-methyl-pyrido[3,4-d]pyrimidine

HRID 2227254Notes

Reaction equation

[CH3:1][C:2]1[N:12]=[CH:11][C:5]2[N:6]=[CH:7][NH:8][C:9](=O)[C:4]=2[CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)(Cl)(Cl)Cl.[Cl:37][C:38]1[CH:46]=[C:45]2[C:41]([CH2:42][CH2:43][NH:44]2)=[CH:40][CH:39]=1>ClCCCl>[Cl:37][C:38]1[CH:46]=[C:45]2[C:41]([CH2:42][CH2:43][N:44]2[C:9]2[C:4]3[CH:3]=[C:2]([CH3:1])[N:12]=[CH:11][C:5]=3[N:6]=[CH:7][N:8]=2)=[CH:40][CH:39]=1

Participants

Conditions

Temperature: 60 °C

Procedure

6Methyl-pyrido[3,4-d]pyrimid-4one (200 mg, 1.24 mmol), polymer-supported triphenylphosphine (2.06 g of 3.0 mmol Pig resin, 6.20 mmol) and anhydrous carbon tetrachloride (1.20 mL, 12.40 mmol) were combined in 1,2-dichloroethane (6 mL). The mixture was heated to 60° C. under an atmosphere of dry N2(g) for 18 hours. 6-Chloroindoline (1.1 eq.) was added and heating was continued at 60° C. for another 18 hours. The triphenyphosphine-bearing resin was filtered off and washed several times with chloroform. The filtrate and washings were concentrated in vacuo and preparative reversed-phase (C18) chromatography utilizing a gradient of 15% to 70% MeCN/pH4.5, 50 mM NH4OAc followed by lyophilization of the appropriate fractions afforded the title product (30%) as its free-base: MP: 232-234° C.; LC-MS: 297 (MH+); anal. RP-HPLC: 4.33 minutes.

Workup

temperatureheating
filtrationThe triphenyphosphine-bearing resin was filtered off
washwashed several times with chloroform
concentrationThe filtrate and washings were concentrated in vacuo

Sources & evidence

ORD record: ord-38fd3f8d32b64abc890c32277956bf7b
Source dataset: uspto-grants-2002_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06413971B1

Reaction notes

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