Diisopropylethylamine → HCID 86726854, compound

HRID 1499635Notes

Reaction equation

HRID 1499635 reaction equation
C(OC([NH:8][C:9]1[S:13][C:12]([C:14]2[C:19]([F:20])=[CH:18][CH:17]=[CH:16][C:15]=2[F:21])=[N:11][C:10]=1[C:22]([OH:24])=O)=O)(C)(C)C.[NH2:25][C:26]1[C:27]([N:35]2[CH2:40][C@H:39]([CH3:41])[C@:38]([OH:43])([CH3:42])[C@H:37]([NH:44]C(=O)OC(C)(C)C)[CH2:36]2)=[C:28]2[CH2:34][CH2:33][O:32][C:29]2=[N:30][CH:31]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[NH2:8][C:9]1[S:13][C:12]([C:14]2[C:15]([F:21])=[CH:16][CH:17]=[CH:18][C:19]=2[F:20])=[N:11][C:10]=1[C:22]([NH:25][C:26]1[C:27]([N:35]2[CH2:40][C@H:39]([CH3:41])[C@:38]([OH:43])([CH3:42])[C@H:37]([NH2:44])[CH2:36]2)=[C:28]2[CH2:34][CH2:33][O:32][C:29]2=[N:30][CH:31]=1)=[O:24]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 674381985-((Tert-butoxycarbonyl)amino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acidHCID 86726852HCID 86726852, compound

Product 1

HCID 86726854HCID 86726854, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 5-[(tert-butoxycarbonyl)amino]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxylic acid (55 mg, 0.15 mmol), tert-butyl [(3R,4R,5S)-1-(5-amino-2,3-dihydrofuro[2,3-b]pyridin-4-yl)-4-hydroxy-4,5-dimethylpiperidin-3-yl]carbamate (44 mg, 0.12 mmol) and HATU (134 mg, 0.353 mmol), DMF (2.0 mL) was added, followed by DIPEA (86 mg, 0.67 mmol). The reaction mixture was stirred at room temperature for 3 h, and then concentrated under reduced pressure. DCM (2.0 mL) was added to the resulting residue followed by TFA (2.0 mL). The mixture was stirred at room temperature for 30 min. and then concentrated under reduced pressure. The resulting residue was purified using RP-HPLC (XBridge™ C18 column, eluting with a gradient of MeCN/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min.) to afford the title compound as a white solid (20 mg, 34%). LCMS calc. for C24H27F2N6O3s (M+H)+: m/z=517.2. found 517.0. 1H NMR (500 MHz, DMSO-d6) δ 9.17 (s, 1H), 8.61 (s, 1H), 7.59-7.45 (m, 3H), 7.21 (t, J=8.6 Hz, 2H), 4.52-4.42 (m, 2H), 4.06 (s, 1H), 3.37 (t, J=8.5 Hz, 2H), 2.99-2.92 (m, 1H), 2.90-2.79 (m, 2H), 2.77-2.64 (m, 2H), 1.93-1.82 (m, 1H), 1.46 (br, 2H), 0.92 (s, 3H), 0.71 (d, J=6.9 Hz, 3H) ppm.

Workup

  1. additionwas added
  2. concentrationconcentrated under reduced pressure
  3. additionDCM (2.0 mL) was added to the resulting residue
  4. stirringThe mixture was stirred at room temperature for 30 min.
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified
  7. washeluting with a gradient of MeCN/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min.)

Sources & evidence

ORD record
ord-2cce2d6132b645c08d325cf46dd8a4c9
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

Loading…