Diisopropylethylamine → HCID 69937522, compound

HRID 2281850Notes

Reaction equation

HRID 2281850 reaction equation
C(N(C(C)C)C(C)C)C.[NH2:10][C:11]1[CH:12]=[CH:13][C:14]([F:37])=[C:15]([C@:17]23[CH2:25][O:24][C@H:23]([CH3:26])[C@H:22]2[C:21](=[O:27])[N:20]([CH3:28])[C:19]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[N:18]3)[CH:16]=1.[CH3:38][O:39][C:40]1[N:41]=[CH:42][C:43]([C:46](O)=[O:47])=[N:44][CH:45]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>C(Cl)Cl>[F:37][C:14]1[CH:13]=[CH:12][C:11]([NH:10][C:46]([C:43]2[CH:42]=[N:41][C:40]([O:39][CH3:38])=[CH:45][N:44]=2)=[O:47])=[CH:16][C:15]=1[C@:17]12[CH2:25][O:24][C@H:23]([CH3:26])[C@H:22]1[C:21](=[O:27])[N:20]([CH3:28])[C:19]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:33])([CH3:35])[CH3:34])=[N:18]2

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 457898115-Methoxy-2-pyrazinecarboxylic acidHCID 69937537HCID 69937537, compound

Product 1

HCID 69937522HCID 69937522, compoundYield 106.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-Ethyl-N-(propan-2-yl)propan-2-amine (0.33 mL, 1.9 mmol) was added to a stirred mixture of tert-butyl ((4aS,5R,7aS)-7a-(5-amino-2-fluorophenyl)-3,5-dimethyl-4-oxo-3,4,4a,5,7,7a-hexahydrofuro[3,4-d]pyrimidin-2-yl)carbamate (150 mg, 0.38 mmol), 5-methoxypyrazine-2-carboxylic acid (89 mg, 0.57 mmol) and (1H-benzotriazol-1-yloxy)(tripyrrolidin-1-yl)phosphonium hexafluorophosphate (300 mg, 0.57 mmol) in dry DCM (2 mL). The mixture was stirred at RT overnight. The reaction mixture was partitioned between DCM and NaHCO3 (aq). The aqueous layer was extracted with DCM (×2). The combined extracts were dried by passing through a hydrophobic frit and then evaporated. The residue was purified by column chromatography (normal phase, 10 g, Biotage SNAP cartridge KP-Sil, 12 mL per min, gradient 5% to 30% EtOAc in n-hexane) to give the title compound (213 mg, foam). 1H NMR (400 MHz, CDCl3) δ ppm 1.52 (d, J=6.06 Hz, 3H) 1.56 (s, 9H) 3.31 (s, 3H) 3.44 (dd, J=9.09, 1.77 Hz, 1H) 4.08 (s, 3H) 4.31 (d, J=9.85 Hz, 1H) 4.37-4.47 (m, 2H) 7.16 (dd, J=10.74, 8.97 Hz, 1H) 7.54 (dd, J=6.82, 2.53 Hz, 1H) 7.84 (ddd, J=8.78, 4.23, 2.65 Hz, 1H) 8.15 (d, J=1.26 Hz, 1H) 9.01 (d, J=1.26 Hz, 1H) 9.49 (s, 1H) 10.60 (s, 1H).

Workup

  1. customThe reaction mixture was partitioned between DCM and NaHCO3 (aq)
  2. extractionThe aqueous layer was extracted with DCM (×2)
  3. customThe combined extracts were dried
  4. customevaporated
  5. customThe residue was purified by column chromatography (normal phase, 10 g, Biotage SNAP cartridge KP-Sil, 12 mL per min, gradient 5% to 30% EtOAc in n-hexane)

Sources & evidence

ORD record
ord-494ff5cc931d4145aaab8b04a7d5fd8c
Source dataset
uspto-grants-2015_09
Patent number
US09139594B2

Reaction notes

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