Trifluoroacetic acid → 5-Amino-N-{4-[(3S)-3-aminopiperidin-1-yl]-2,3-dihydrofuro[2,3-b]pyridin-5-yl}-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide

HRID 1499427Notes

Reaction equation

HRID 1499427 reaction equation
C(O)(C(F)(F)F)=O.C(OC([NH:15][C:16]1[S:20][C:19]([C:21]2[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=2[F:28])=[N:18][C:17]=1[C:29]([NH:31][C:32]1[C:33]([N:41]2[CH2:46][CH2:45][CH2:44][C@H:43]([NH:47]C(=O)OC(C)(C)C)[CH2:42]2)=[C:34]2[CH2:40][CH2:39][O:38][C:35]2=[N:36][CH:37]=1)=[O:30])=O)(C)(C)C>C(Cl)Cl>[NH2:15][C:16]1[S:20][C:19]([C:21]2[C:22]([F:28])=[CH:23][CH:24]=[CH:25][C:26]=2[F:27])=[N:18][C:17]=1[C:29]([NH:31][C:32]1[C:33]([N:41]2[CH2:46][CH2:45][CH2:44][C@H:43]([NH2:47])[CH2:42]2)=[C:34]2[CH2:40][CH2:39][O:38][C:35]2=[N:36][CH:37]=1)=[O:30]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86726678tert-Butyl {(3S)-1-[5-({[5-[(tert-butoxycarbonyl)amino]-2-(2,6-difluorophenyl)-1,3-thiazol-4-yl]carbonyl}amino)-2,3-dihydrofuro[2,3-b]pyridin-4-yl]piperidin-3-yl}carbamate

Product 1

HCID 762848285-Amino-N-{4-[(3S)-3-aminopiperidin-1-yl]-2,3-dihydrofuro[2,3-b]pyridin-5-yl}-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamideYield 37.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (3.0 mL) was added to a solution of tert-butyl {(3S)-1-[5-({[5-[(tert-butoxycarbonyl)amino]-2-(2,6-difluorophenyl)-1,3-thiazol-4-yl]carbonyl}amino)-2,3-dihydrofuro[2,3-b]pyridin-4-yl]piperidin-3-yl}carbamate (720.2 mg, 1.070 mmol) in DCM (3.0 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 0.15% NH4OH, at flow rate of 30 mL/min.) to give the title compound as a white solid (187.7 mg, 37%). LCMS calc. for C22H23F2N6O2S (M+H)+: m/z=473.1. found 473.2. 1H NMR (500 MHz, DMSO-d6) δ 8.74 (s, 1H), 7.68-7.39 (m, 3H), 7.26 (t, J=8.8 Hz, 2H), 4.48 (t, J=8.9 Hz, 2H), 3.37 (t, J=8.5 Hz, 2H), 3.14-3.01 (m, 1H), 3.00-2.90 (m, 1H), 2.89-2.81 (m, 1H), 2.77-2.69 (m, 1H), 2.55-2.50 (m, 1H), 1.83-1.59 (m, 3H), 1.12-1.00 (m, 1H) ppm.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe resulting residue was purified
  3. washeluting with a gradient of MeCN/water containing 0.15% NH4OH, at flow rate of 30 mL/min.)

Sources & evidence

ORD record
ord-0c294075ce1a4f3b9b960562b80e20b8
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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