Trifluoroacetic acid → HCID 86726691, compound

HRID 1499447Notes

Reaction equation

HRID 1499447 reaction equation
[NH2:1][C:2]1[C:3]([N:11]2[CH2:16][CH2:15][CH2:14][C@H:13]([NH:17]C(=O)OC(C)(C)C)[CH2:12]2)=[C:4]2[CH2:10][CH2:9][CH2:8][C:5]2=[N:6][CH:7]=1.C(OC([NH:32][C:33]1[S:37][C:36]([C:38]2[C:43]([F:44])=[CH:42][CH:41]=[CH:40][C:39]=2[F:45])=[N:35][C:34]=1[C:46](O)=[O:47])=O)(C)(C)C.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.C(O)(C(F)(F)F)=O>CN(C=O)C>[NH2:32][C:33]1[S:37][C:36]([C:38]2[C:43]([F:44])=[CH:42][CH:41]=[CH:40][C:39]=2[F:45])=[N:35][C:34]=1[C:46]([NH:1][C:2]1[C:3]([N:11]2[CH2:16][CH2:15][CH2:14][C@H:13]([NH2:17])[CH2:12]2)=[C:4]2[CH2:10][CH2:9][CH2:8][C:5]2=[N:6][CH:7]=1)=[O:47]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 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 86726688tert-Butyl [(3S)-1-(3-amino-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)piperidin-3-yl]carbamate

Product 1

HCID 86726691HCID 86726691, compoundYield 35.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of tert-butyl [(3S)-1-(3-amino-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)piperidin-3-yl]carbamate (15 mg, 0.045 mmol), 5-[(tert-butoxycarbonyl)amino]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxylic acid (19 mg, 0.054 mmol), HATU (43 mg, 0.11 mmol) and DIPEA (24 μL, 0.14 mmol) in dry DMF (0.11 mL) was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure to give an intermediate, which was treated with TFA (0.070 mL, 0.90 mmol). The resulting reaction mixture was stirred at room temperature for 1 h then concentrated under reduced pressure. The residue was diluted with MeOH and neutralized with small amount of NH4OH. The mixture was filtered and purified by preparative LC-MS (XBridge™ preparative C18 5 μm 30×10 mm OBD™ column, flow rate 60 mL/min., eluting with a gradient of MeCN and water with 1.5% NH4OH) to give the title compound as a white powder (7.5 mg, 35%). LCMS calc. for C23H25F2N6OS (M+H)+: m/z=471.2. Found: 471.1. 1H NMR (500 MHz, DMSO-d6) δ 9.24 (s, 1H), 7.61 (s, 2H), 7.57-7.45 (m, 1H), 7.36-7.17 (m, 2H), 3.12-2.96 (m, 3H), 2.91 (t, J=9.8 Hz, 1H), 2.88-2.70 (m, 4H), 2.66-2.55 (m, 1H), 2.07-1.99 (m, 2H), 1.86-1.56 (m, 3H), 1.18-1.01 (m, 1H) ppm.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto give an intermediate, which
  3. customThe resulting reaction mixture
  4. stirringwas stirred at room temperature for 1 h
  5. concentrationthen concentrated under reduced pressure
  6. additionThe residue was diluted with MeOH and neutralized with small amount of NH4OH
  7. filtrationThe mixture was filtered
  8. custompurified by preparative LC-MS (XBridge™ preparative C18 5 μm 30×10 mm OBD™ column, flow rate 60 mL/min.
  9. washeluting with a gradient of MeCN and water with 1.5% NH4OH)

Sources & evidence

ORD record
ord-ff50fec1936b4e22b12c6bf7ca772b1e
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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