Trifluoroacetic acid → HCID 178488304, compound

HRID 2200529Notes

Reaction equation

HRID 2200529 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@:9]23[N:33]([C:34]([C:36]4[C:37]([CH3:41])=[N:38][O:39][CH:40]=4)=[O:35])[CH2:32][CH2:31][N:10]2[C:11](=[O:30])[C:12]2[N:13]([C:15]4[N:20]=[C:19]([CH3:21])[N:18](COCC[Si](C)(C)C)[C:16]=4[CH:17]=2)[CH2:14]3)=[CH:5][CH:4]=1.COC1C=CC([C@]23N(C(C4C(C)=NOC=4)=O)CCN2C(=O)C2N(C4N(COCC[Si](C)(C)C)C=NC=4C=2)C3)=CC=1.FC(F)(F)C(O)=O>ClCCl>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]23[N:33]([C:34]([C:36]4[C:37]([CH3:41])=[N:38][O:39][CH:40]=4)=[O:35])[CH2:32][CH2:31][N:10]2[C:11](=[O:30])[C:12]2[N:13]([C:15]4[NH:20][C:19]([CH3:21])=[N:18][C:16]=4[CH:17]=2)[CH2:14]3)=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 86716524HCID 86716524, compoundHCID 86716525HCID 86716525, compound

Product 1

HCID 178488304HCID 178488304, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Either (5aS)-5a-(4-methoxyphenyl)-2-methyl-6-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-5a,6,7,8-tetrahydro-5H-imidazo[1,2-a]imidazo[4′,5′:4,5]pyrrolo[1,2-d]pyrazin-10(1H)-one or its regioisomer (5aS)-5a-(4-methoxyphenyl)-6-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-3-{[2-(trimethylsilyl)ethoxy]methyl}-5a,6,7,8-tetrahydro-5H-imidazo[1,2-a]imidazo[4′,5′:4,5]pyrrolo[1,2-d]pyrazin-10(3H)-one (27 mg, 0.048 mmol) similarly prepared according to steps (a), (b) and (c) was dissolved in dichloromethane (0.9 mL) and treated with trifluoro acetic acid (2.1 mL). The mixture was stirred at room temperature. After one hour the LCMS indicated complete deprotection. The mixture was then concentrated in vacuo and the residue obtained purified by flash chromatography using the biotage SP4 (0-5% MeOH gradient in EtOAc) to yield either 5a-(4-methoxyphenyl)-2-methyl-6-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-5a,6,7,8-tetrahydro-5H-imidazo[1,2-a]imidazo[4′,5′:4,5]pyrrolo[1,2-d]pyrazin-10(1H)-one (2) or its regioisomer 5a-(4-methoxyphenyl)-2-methyl-6-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-5a,6,7,8-tetrahydro-5H-imidazo[1,2-a]imidazo[4′,5′:4,5]pyrrolo[1,2-d]pyrazin-10(3H)-one (8.5 mg, 40% yield). ESI-MI m/z [M+H]+ 447.09. 1H NMR (400 MHz, CDCl3) δ 8.53 (br s, 1H), 8.46 (br s, 1H), 7.43 (br d, J=8.9 Hz, 2H), 6.82-6.73 (m, 2H), 6.69 (s, 1H), 6.05 (d, J=13.1 Hz, 1H), 4.46 (d, J=12.8 Hz, 1H), 4.35 (ddd, J=10.7, 8.8, 4.6 Hz, 1H), 4.00 (td, J=8.9, 5.6 Hz, 1H), 3.83 (tdd, J=13.2, 9.8, 6.6 Hz, 2H), 3.72 (s, 3H), 2.52 (s, 3H), 2.42 (d, J=0.5 Hz, 3H). The compounds in Table 1 were similarly prepared by reference to the general method(s) and/or synthetic examples.

Workup

  1. concentrationThe mixture was then concentrated in vacuo
  2. customthe residue obtained
  3. custompurified by flash chromatography

Sources & evidence

ORD record
ord-c44b8d22f94b43e39564fd29e78b8f49
Source dataset
uspto-grants-2016_06
Patent number
US09359377B2

Reaction notes

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