Hydrochloric Acid → HCID 68651306, compound

HRID 646776Notes

Reaction equation

HRID 646776 reaction equation
[NH2:1][C:2]1[C:3]([C:27]([OH:29])=O)=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([NH:16][C@H:17]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH2:19][C@@H:18]3[OH:26])=[O:15])[CH:9]=2)=[CH:6][N:7]=1.[C:30]1([CH2:36][N:37]2[CH2:43][CH2:42][CH2:41][CH2:40][C@H:39]([NH2:44])[CH2:38]2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.Cl>CN(C=O)C.C1COCC1.C(OCC)(=O)C.CCOCC>[NH2:1][C:2]1[C:3]([C:27]([NH:44][C@H:39]2[CH2:40][CH2:41][CH2:42][CH2:43][N:37]([CH2:36][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH2:38]2)=[O:29])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([NH:16][CH:17]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH2:19][C@@H:18]3[OH:26])=[O:15])[CH:9]=2)=[CH:6][N:7]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 57463512HCID 57463512, compoundHCID 68651875HCID 68651875, compound

Product 1

HCID 68651306HCID 68651306, compoundYield 12%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolventHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

3-Amino-6-[3-({[(1S,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]pyrazine-2-carboxylic acid (1.0 eq) was dissolved in DMF-THF and treated with (3S)-1-(phenylmethyl)azepan-3-amine (1.46 eq), EDCI (1.2 eq) and HOBt (1.2 eq) at ambient temperature. After being stirred overnight, the reaction mixture was quenched by addition of aqueous sodium bicarbonate followed by extraction with ethyl acetate (20 mL×3). The aqueous phase was extracted once with additional ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride then dried over anhydrous magnesium sulfate. Filtration and concentration in vacuo gave a crude oil, which was purified by preparative HPLC to yield a crude oil, which was dissolved in ethyl acetate (10 mL), and treated with 1M HCl in ether (5 mL). The resulting precipitation was filtered, washed with methanol (2×20 mL), and dried to afford 122 mg (12% yield) of 3-amino-6-[3-({[(2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino}carbonyl)phenyl]-N-[(3S)-1-(phenylmethyl)azepan-3-yl]pyrazine-2-carboxamide (122 mg, 15% yield).: 1H NMR (400 MHz, DMSO-d6): δ 8.98 (s, 1H), 8.90 (m, 1H), 8.75 (s, 1H), 8.63 (m, 2H), 8.11 (m, 1H), 7.95 (m, 2H), 7.62 (m, 2H), 7.58 (m, 1H), 7.42 (m, 1H), 7.20 (m, 3H), 7.08 (m, 1H), 5.50 (m, 1H), 4.51 (m, 1H), 4.49 (m, 1H), 4.46 (m, 1H), 4.40 (m, 1H), 3.50 (m, 1H), 3.65 (m, 2H), 3.20 (m, 2H), 2.85 (m, 1H), 2.10 (m, 1H), 1.80 (m, 2H), 1.58 (m, 1H); MS (EI) for C34H36N6O3: 577.08 (MH+).

Workup

  1. customthe reaction mixture was quenched by addition of aqueous sodium bicarbonate
  2. extractionfollowed by extraction with ethyl acetate (20 mL×3)
  3. extractionThe aqueous phase was extracted once with additional ethyl acetate
  4. washThe combined organic layers were washed with saturated aqueous sodium chloride
  5. dry with materialthen dried over anhydrous magnesium sulfate
  6. filtrationFiltration and concentration in vacuo
  7. customgave a crude oil, which
  8. customwas purified by preparative HPLC
  9. customto yield a crude oil, which
  10. customThe resulting precipitation
  11. filtrationwas filtered
  12. washwashed with methanol (2×20 mL)
  13. customdried

Sources & evidence

ORD record
ord-d653be2c2f6a44c8805a363c97ac18af
Source dataset
uspto-grants-2010_04
Patent number
US07704995B2

Reaction notes

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