Hydrochloric Acid → HCID 59200358, compound

HRID 1685354Notes

Reaction equation

HRID 1685354 reaction equation
[F:1][C:2]1[C:3]([C:28]([NH:30][CH2:31][C:32]([OH:42])([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH2:33][CH2:34][CH3:35])=[O:29])=[N:4][CH:5]=[CH:6][C:7]=1[S:8][C:9]1[S:13][C:12]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([NH:21][CH:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)=[CH:17][N:16]=2)=[N:11][CH:10]=1.[CH3:43][N:44]([CH3:49])[CH2:45][C:46](O)=[O:47].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.Cl>CN1C(=O)CCC1>[CH3:43][N:44]([CH3:49])[CH2:45][C:46]([N:25]1[CH2:24][CH2:23][CH:22]([NH:21][C:18]2[CH:19]=[CH:20][C:15]([NH:14][C:12]3[S:13][C:9]([S:8][C:7]4[CH:6]=[CH:5][N:4]=[C:3]([C:28]([NH:30][CH2:31][C:32]([OH:42])([C:36]5[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=5)[CH2:33][CH2:34][CH3:35])=[O:29])[C:2]=4[F:1])=[CH:10][N:11]=3)=[N:16][CH:17]=2)[CH2:27][CH2:26]1)=[O:47]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 673N,N-DimethylglycineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 59200462HCID 59200462, compound

Product 1

HCID 59200358HCID 59200358, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a stirring suspension of 3-fluoro-N-(2-hydroxy-2-phenylpentyl)-4-(2-(5-(piperidin-4-ylamino)pyridin-2-ylamino)thiazol-5-ylthio)picolinamide (737 mg, 1.021 mmol), dimethylglycine (636 mg, 6.167 mmol), EDAC (590 mg, 3.078 mmol), HOBt (275 mg, 2.035 mmol) in NMP (10 mL) was added i-Pr2Net (1.8 ml, 10.3 mmol). After 2 h, the reaction was diluted with PrepLC solvent B (TFA):TFA (8 mL:2 mL), filtered into 14 prepLC vials, purified on PrepLC (YMC-Pack C18 30×100 mm, NH4Oac). The fractions containing the product were concentrated in SpeedVac overnight. The fractions were pooled together using MeOH and concentrated. The product was obtained (417 mg, 59%) as a solid, then converted to the HCl salt: 1H NMR (400 MHz, DMSO-d6) δ ppm: 11.52 (1H, s), 9.53 (1H, s), 8.23 (2H, t, J=5.81 Hz), 7.78 (1H, s), 7.72 (1H, s), 7.42 (2H, d, J=7.33 Hz), 7.29 (2H, t, J=7.58 Hz), 7.18 (2H, t, J=7.33 Hz), 7.03 (1H, t, J=5.31 Hz), 6.96 (1H, d, J=8.84 Hz), 4.29 (2H, m), 3.61 (3H, d, J=5.81 Hz), 3.15 (1H, m), 2.93 (1H, t, J=11.62 Hz), 2.75-2.82 (6H, m), 1.95 (3H, t, J=9.98 Hz), 1.65-1.78 (2H, m), 1.33 (2H, s), 1.17-1.26 (2H, m), 0.88 (1H, m), 0.74 (3H, t, J=7.20 Hz); LC/MS (M+H)+: 693. HPLC ret. time (Condition M): 1.40 min.

Workup

  1. additionwas added i-Pr2Net (1.8 ml, 10.3 mmol)
  2. filtrationTFA (8 mL:2 mL), filtered into 14 prepLC vials
  3. custompurified on PrepLC (YMC-Pack C18 30×100 mm, NH4Oac)
  4. additionThe fractions containing the product
  5. concentrationwere concentrated in SpeedVac overnight
  6. concentrationconcentrated
  7. customThe product was obtained (417 mg, 59%) as a solid
  8. custom1.40 min.

Sources & evidence

ORD record
ord-d08d3a124991487fa278ddbdd3aea325
Source dataset
uspto-grants-2012_04
Patent number
US08148400B2

Reaction notes

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