Thionyl Chloride → 6-[4-(Chloromethyl)phenyl]-N-((R)-1-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

HRID 133025Notes

Reaction equation

S(Cl)([Cl:3])=O.[C:5]1([C@H:11]([NH:13][C:14]2[C:15]3[CH:22]=[C:21]([C:23]4[CH:28]=[CH:27][C:26]([CH2:29]O)=[CH:25][CH:24]=4)[NH:20][C:16]=3[N:17]=[CH:18][N:19]=2)[CH3:12])[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1>C1(C)C=CC=CC=1>[Cl:3][CH2:29][C:26]1[CH:25]=[CH:24][C:23]([C:21]2[NH:20][C:16]3[N:17]=[CH:18][N:19]=[C:14]([NH:13][C@@H:11]([C:5]4[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=4)[CH3:12])[C:15]=3[CH:22]=2)=[CH:28][CH:27]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of thionyl chloride (25.7 ml, 0.328 mol) in 180 ml of toluene is cooled to −10° C. Solid {4-[4-((R)-1-phenyl-ethylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-phenyl}-methanol (11.3 g, 0.0328 mol) is added in 8 portions over a range of 1 h. The temperature is then increased slowly to 0° C. and the mixture stirred for 2 h. The cold reaction mixture is filtered and the solid washed with toluene and ether. The crude product is suspended in water and treated with saturated sodium bicarbonate solution until the mixture turns basic. The mixture is stirred well for about 10 min and filtered. The solid is thoroughly washed with water and dried under reduced pressure to give the title compound; m.p.>320° C.; Rf (dichloromethane/ethanol 9:1)=0.46; HPLC tR=10.63 min; MS-ES+: (M+H)+=363.

Workup

customThe cold reaction mixture
filtrationis filtered
washthe solid washed with toluene and ether
additiontreated with saturated sodium bicarbonate solution until the mixture
stirringThe mixture is stirred well for about 10 min
filtrationfiltered
washThe solid is thoroughly washed with water
customdried under reduced pressure

Sources & evidence

ORD record: ord-8ae97f1d1ada4e3a8ace7112f691ae45
Source dataset: uspto-grants-2008_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07390805B2

Reaction notes

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