Sodium triacetoxyborohydride → (S)-1-(4-((2-chloro-7-methyl-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one

HRID 341309Notes

Reaction equation

HRID 341309 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:5]2[S:10][C:9]([CH:11]=O)=[C:8]([CH3:13])[C:6]=2[N:7]=1.[OH:20][C@@H:21]([CH3:30])[C:22]([N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1)=[O:23].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].B.N1C=CC=CC=1C.B.C(C1C=CC(C)=NC=1)C>>[Cl:1][C:2]1[N:3]=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:5]2[S:10][C:9]([CH2:11][N:27]3[CH2:26][CH2:25][N:24]([C:22](=[O:23])[C@@H:21]([OH:20])[CH3:30])[CH2:29][CH2:28]3)=[C:8]([CH3:13])[C:6]=2[N:7]=1

Participants

6

Reactant 5

HCID 5049666Sodium triacetoxyborohydrideHCID 16217944Borane;2-methylpyridineHCID 566485822-Chloro-7-methyl-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde2×HCID 68437343(S)-2-hydroxy-1-(piperazin-1-yl)propan-1-oneHCID 178419175HCID 178419175, compound

Product 1

HCID 86623526(S)-1-(4-((2-chloro-7-methyl-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one

Procedure

Scheme 2 shows the synthesis of intermediate (S)-1-(4-((2-chloro-7-methyl-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one II from 4-(2-chloro-7-methylthieno[3,2-d]pyrimidin-4-yl)morpholino VI. Treatment of VI with isopropylmagnesium chloride Grignard reagent followed by n-butyllithium at −10° C. was followed by addition of dimethylformamide and quenching with aqueous acid gave formylated intermediate 2-chloro-7-methyl-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde IV (Example 4). Reductive amination of IV was effected by mixing IV with the oxalate salt of (S)-2-hydroxy-1-(piperazin-1-yl)propan-1-one V followed by a reducing agent, such as sodium triacetoxyborohydride (Method A), 2-picoline borane (Method B) or 5-Ethyl-2-methylpyridine borane to give II which was crystallized in toluene/heptane (Example 5) or Me-THF/heptane.

Sources & evidence

ORD record
ord-cb5040194e574905a938d2f91e3025c9
Source dataset
uspto-grants-2014_11
Patent number
US08895729B2

Reaction notes

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