Diisopropylethylamine → HCID 178431862, compound

HRID 58265Notes

Reaction equation

HRID 58265 reaction equation
[NH2:1][CH:2]([C:4]1[N:5]=[C:6]2[S:21][CH:20]=[C:19]([CH3:22])[N:7]2[C:8](=[O:18])[C:9]=1[C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[C:12]([F:17])[CH:11]=1)[CH3:3].[NH2:23][C:24]1[N:32]=[C:31]2[C:27]([NH:28][CH:29]=[N:30]2)=[C:26](Br)[N:25]=1.C(N(CC)C(C)C)(C)C>C(O)C>[NH2:23][C:24]1[N:32]=[C:31]2[C:27]([N:28]=[CH:29][NH:30]2)=[C:26]([NH:1][CH:2]([C:4]2[N:5]=[C:6]3[S:21][CH:20]=[C:19]([CH3:22])[N:7]3[C:8](=[O:18])[C:9]=2[C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[C:12]([F:17])[CH:11]=2)[CH3:3])[N:25]=1

Participants

5

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 61011392-Amino-6-bromopurine3×HCID 581114097-(1-aminoethyl)-6-(3,5-difluorophenyl)-3-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one

Product 1

HCID 178431862HCID 178431862, compoundYield 52.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of optical pure 7-(1-aminoethyl)-6-(3,5-difluorophenyl)-3-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one (0.13 g, 0.40 mmol) made from above, 2-amino-6-bromopurine (0.10 g, 0.47 mmol), and N,N-diisopropylethylamine (0.085 mL, 0.49 mmol) in ethanol (1 mL) was heated at 110° C. overnight. LCMS showed incomplete conversion. An additional 0.5 equivalent of 2-amino-6-bromopurine and 1.0 equivalent of N,N-diisopropylethylamine was added, and the mixture was stirred at 110° C. for another day. The solid was shown to be 2-amino-6-bromopurine by LCMS. The mixture was filtered, and the filtrates were purified on preparative-LCMS ((XBridge C18 Column, eluting with a gradient of acetonitrile/water containing 0.15% NH4OH) to give the desired product (0.095 g, 52%). LCMS calculated for C20H17F2N8OS (M+H)+: m/z=455.1. Found: 455.1 1H NMR (DMSO-d6, 400 MHz) δ 7.67 (1H, s), 7.27 (1H, m), 7.17 (3H, m), 7.07 (1H, s), 6.89 (1H, br s), 5.45 (2H, br s), 5.03 (1H, m), 2.63 (3H, s), 1.30 (3H, d, J=6.8 Hz) ppm. 19F NMR (DMSO-d6, 376.3 MHz) δ −111 ppm.

Workup

  1. filtrationThe mixture was filtered
  2. customthe filtrates were purified on preparative-LCMS ((XBridge C18 Column
  3. washeluting with a gradient of acetonitrile/water containing 0.15% NH4OH)

Sources & evidence

ORD record
ord-e1abc11a2c7c46f68fa60daa59bebd2f
Source dataset
uspto-grants-2016_09
Patent number
US09434746B2

Reaction notes

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