Reaction SMILES: [N:1]1[C:6]2[CH:7]=[CH:8][O:9][C:5]=2[C:4]([NH2:10])=[N:3][C:2]=1N.[Cl:12]C1N=C(Cl)C2OC=CC=2N=1>>[Cl:12][C:2]1[N:3]=[C:4]([NH2:10])[C:5]2[O:9][CH:8]=[CH:7][C:6]=2[N:1]=1
Reactant: Clc1nc(Cl)c2occc2n1
Reactant: Nc1nc(N)c2occc2n1
Product: Nc1nc(Cl)nc2ccoc12

Procedure:
Methods for preparing furo[3,2-d]pyrimidine-2,4-diamine compounds 5 of the invention are illustrated in Scheme I. In Scheme I, commercially available 2,4-dichlorofuro[3,2-d]pyrimidine (ArkPharm) 1 may be reacted with an amine 2 (Scheme I, step a) as described in General Procedure A to give a 2-chlorofuro[3,2-d]pyrimidin-4-amine 3 that is substituted with an Ra and Rb substituent. Subsequent reaction with a primary amine 4 (Scheme I, step b) using Buchwald coupling conditions as described by General Procedure B would give a furo[3,2-d]pyrimidine-2,4-diamine 5. Alternatively, this transformation can be accomplished with a 2-chlorofuro[3,2-d]pyrimidin-4-amine 3, a primary amine 4 and an acid source, such as TFA, HCl or AcOH with or without heating to give a furo[3,2-d]pyrimidine-2,4-diamine 5. The amines 2 and/or 4 are either commercially available or can be prepared by methods known to one skilled in the art (see, for example, Larock, R. C. “Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 2nd edition”, 1999, Wiley-VCH or the General Procedures below). Further functionalization of any of the intermediates, for instance compounds 2, 3 and/or 4 in Scheme I, and/or the furo[3,2-d]pyrimidine-2,4-diamine compounds 5 can be performed with appropriate functionality on Ra, Rb and/or R3, if desired, using reactions known to one skilled in the art (see, for example, Larock, R. C. [referenced above] or the General Procedures below). For example, formation of amides or sulfonamides can be achieved by reaction of a primary or secondary amine with either acid halides or carboxylic acids or alternatively a sulfonyl chloride (see, for example, General Procedures D, E.1 and E.2). Additionally, amides could be prepared by the saponification of esters to a carboxylic acid (see, for example, General Procedure AI) and then subsequent reaction with primary or secondary amines by the methods described above for amide formation. Amino alcohols can be cyclized to carbamates (see, for example, General Procedures AL). Amines can be prepared in many ways known to one skilled in the art. For example nitro groups can be reduced to primary amines (see, for example, General Procedures I) Amines can be formed by conversion of alcohols to mesylates (see, for example, General Procedures V) which can then be substituted with amines (see, for example, General Procedures U) directly or converted to the azide which is then reduced (see, for example, General Procedures F) to provide an amine. Alternately, alcohols can be oxidized to the ketone or aldehyde (see, for example, General Procedure P) which may then be converted by reductive amination with a primary or secondary amine (see, for example, General Procedure H) to give amines. Additionally, nitriles may be converted to amines by reduction (see, for example, General Procedure AE). Nitriles may be obtained from aldehydes (see, for example, General Procedure AA). Alcohols may be obtained from reduction of an ester to provide the alcohol (see, for example, General Procedure W). Additionally, alcohols may be obtained by the reaction of ketones or aldehydes with Grignard reagents (see, for example WO2010138487, Reagent Preparation 5) or also by reduction of ketones or aldehydes with reducing agents (see, for example WO20110092475, Intermediate 39a or European Journal of Organic Chemistry 2009, (9), 1372). Aryl or heteroaryls bearing a halide may be coupled with an aryl or heteroaryl boronate or boronic acid (see, for example, General Procedure Z). Intermediates or final compounds may be further functionalized by alkylation a to a nitrile (see, for example, General Procedure AF or Bioorganic & Medicinal Chemistry Letters 2010, 20(2), 608) or ester (for example a fluorination, General Procedure X or WO 2008108957). Additionally, carbamates may be alkylated (see, for example, General Procedures L). For Scheme I, in certain cases intermediates or in the synthesis of starting materials 2 and 4 may require protection using conditions such as those described in Greene, T. W. and Wuts, P. G. M. [referenced above]. For example, a Boc (see, for example, General procedure O) or Cbz (see, for example, General procedure O) group can be used to form a protected amine Heteroaryl nitrogens can be protected with Boc (see, for example, General procedure O), tosyl (see, for example, General Procedure AJ), SEM (see, for example, General Procedure N), or THP (see, for example, General Procedure AB). Alcohols may be protected as ethers (see, for example, Journal of Medicinal Chemistry 2008, 51(20), 6538 or 2011, 54(3), 869) or as silyl ethers (see, for example, General Procedure AH). Also, deprotection of compounds 5, as well as intermediates 2, 3 and/or 4 containing a protected primary or secondary amine to yield unprotected compounds can be performed using conditions such as those described in Greene, T. W. and Wuts, P. G. M. “Protective Groups in Organic Synthesis, 3rd Edition”, 1999, Wiley-Interscience or in General Procedures C, G, J, K, S, T, AN or AC. For example, a protecting group such as a Boc can be removed from a protected amine to yield the unprotected amine (see, for example, General Procedure C or Example #3, Step E) and the deprotected compounds 5 may then be reacted further as described above. Additionally, a cyclic carbamate can be hydrolyzed to give an aminoalcohol using conditions described in General Procedure AM. Also, deprotection of compounds 5 as well as intermediates 2, 3 and/or 4 containing a silyl protected alcohol to yield unprotected compounds can be performed using conditions such as those described in Greene, T. W. and Wuts, P. G. M. [referenced above] or General Procedure R. In some cases, the deprotection of multiple protecting groups of a different nature may be removed simultaneously as described in General Procedures Q, AD, AG, and AK. For example, deprotection of a protected diamine compound containing both a Boc group and a SEM group can be performed using General Procedure Q to give the unprotected diamine (for example, see Example #5, Step E).