Hydrochloric Acid → (S)-1-((S)-4-((2-(6-aminopyridin-3-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-3-methylpiperazin-1-yl)-2-hydroxypropan-1-one

HRID 390907Notes

Reaction equation

HRID 390907 reaction equation
ClC1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17]OCC2)[C:5]2SC(C=O)=C[C:6]=2N=1.C(N1CCN[C@@H](C)C1)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.Cl.[OH-].[Na+].C[C@H]1CNCCN1CC1N=C(N2CCOCC2)C2SC=CC=2N=1.C(O)(=O)C(C)O.Cl[C:78]1[N:79]=[C:80]([N:100]2[CH2:105][CH2:104][O:103][CH2:102][CH2:101]2)[C:81]2[S:86][C:85]([CH2:87][N:88]3[CH2:93][CH2:92][N:91]([C:94](=[O:98])[C@@H:95]([OH:97])[CH3:96])[CH2:90][C@@H:89]3[CH3:99])=[CH:84][C:82]=2[N:83]=1.CC1(C)C(C)(C)OB(C2C=CC(N)=NC=2)O1>CO>[NH2:3][C:4]1[N:13]=[CH:18][C:17]([C:78]2[N:79]=[C:80]([N:100]3[CH2:105][CH2:104][O:103][CH2:102][CH2:101]3)[C:81]3[S:86][C:85]([CH2:87][N:88]4[CH2:93][CH2:92][N:91]([C:94](=[O:98])[C@@H:95]([OH:97])[CH3:96])[CH2:90][C@@H:89]4[CH3:99])=[CH:84][C:82]=3[N:83]=2)=[CH:6][CH:5]=1

Participants

10

Reactant 8

HCID 313Hydrochloric AcidHCID 612Lactic AcidHCID 14798Sodium HydroxideHCID 27565555-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 7171814(S)-4-N-Trityl-2-methyl-piperazineHCID 457899852-Chloro-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehydeHCID 86623524(S)-1-((S)-4-((2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-3-methylpiperazin-1-yl)-2-hydroxypropan-1-oneHCID 131728701((S)-2-methylpiperazin-1-yl)methyl-4-morpholinothieno[3,2-d]pyrimidine

Product 1

HCID 58233889(S)-1-((S)-4-((2-(6-aminopyridin-3-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-3-methylpiperazin-1-yl)-2-hydroxypropan-1-oneYield 14.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2-Chloro-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde 10 from Example 3 (200 mg) was used according to General Procedure B-3 with (S)-4-N-trityl-2-methyl-piperazine. The crude product was then dissolved in 10 mL of methanol and reacted with 0.5 mL of concentrated HCl for several hours before basifying with NaOH and extracting into EtOAc. After evaporation the crude reaction mixture containing 200 mg of 2-chloro-6-(((S)-2-methylpiperazin-1-yl)methyl-4-morpholinothieno[3,2-d]pyrimidine was reacted with lactic acid via General Procedure B-2. 120 mg of (S)-1-((S)-4-((2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)-3-methylpiperazin-1-yl)-2-hydroxypropan-1-one was reacted with 88 mg of 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine via General Procedure A to give 19.6 mg of 193. MS (Q1) 498.3 (M)+.

Workup

  1. extractionextracting into EtOAc
  2. customAfter evaporation the crude
  3. customreaction mixture

Sources & evidence

ORD record
ord-74ec09d88c604c4395f80d33979a547a
Source dataset
uspto-grants-2013_02
Patent number
US08383620B2

Reaction notes

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