Diisopropylethylamine → HCID 59160879, compound

HRID 415954Notes

Reaction equation

HRID 415954 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1([C:12]2[CH:20]=[CH:19][C:15]([C:16]([OH:18])=O)=[CH:14][CH:13]=2)[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1.C(OC(=O)[NH:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[S:35][CH:36]=[CH:37][CH:38]=2)=[CH:30][C:29]=1[NH2:39])(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>CN(C=O)C>[NH2:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[S:35][CH:36]=[CH:37][CH:38]=2)=[CH:30][C:29]=1[NH:39][C:16](=[O:18])[C:15]1[CH:19]=[CH:20][C:12]([C:6]2([C:2]3[S:1][CH:5]=[CH:4][N:3]=3)[CH2:11][CH2:10][O:9][CH2:8][CH2:7]2)=[CH:13][CH:14]=1

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 57717474tert-Butyl (2-amino-4-(thiophen-2-yl)phenyl)carbamateHCID 59160908HCID 59160908, compound

Product 1

HCID 59160879HCID 59160879, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
45 °C

Procedure

A solution of 4-(4-thiazol-2-yl-tetrahydro-pyran-4-yl)-benzoic acid (0.9 g, 3.11 mmol), 2-Amino-4-thiophen-2-yl-phenyl-carbamic acid tert-butyl ester (1.08 g, 1.1 eq), HATU (1.42 g, 1.2 eq), and DIPEA (1.04 mL, 2.0 eq) were dissolved in DMF and stirred at 45° C. overnight. After the reaction was complete, it was cooled down and precipitated with water and a saturated solution of NaHCO3. The solid formed was collected and used for next step without further purification. Solid {2-[4-(4-thiazol-2-yl-tetrahydro-pyran-4-yl)-benzoylamino]-4-thiophen-2-yl-phenyl}-carbamic acid tert-butyl ester was re-dissolved in DCM/TFA (1:1) and stirred for 1 hour. After the reaction was complete, the reaction mixture was evaporated and purified by reverse phase chromatography to afford title compound, Example 64. MS found for C28H26N7FOS as (M+H)+ 461.12. 1H NMR (400 MHz, dmso-d6): 1H-NMR (DMSO) δ: 9.74 (s, 1H), 8.04 (d, J=8.0 Hz, 2H), 7.67 (d, J=8.8 Hz, 2H), 7.44 (s, 1H), 7.32 (d, J=5.2 Hz, 1H), 7.27 (d, J=8.4 Hz, 1H), 7.21 (d, J=3.6 Hz, 1H), 7.01 (q, J=3.6, 4.8 Hz, 1H), 6.78 (d, J=8.4 Hz, 1H), 5.14 (s, 1H), 4.02-4.00 (m, 2H), 3.69-3.65 (m, 2H), 2.11-2.08 (m, 4H).

Workup

  1. temperatureit was cooled down
  2. customprecipitated with water
  3. customThe solid formed
  4. customwas collected
  5. customused for next step without further purification
  6. dissolutionSolid {2-[4-(4-thiazol-2-yl-tetrahydro-pyran-4-yl)-benzoylamino]-4-thiophen-2-yl-phenyl}-carbamic acid tert-butyl ester was re-dissolved in DCM/TFA (1:1)
  7. stirringstirred for 1 hour
  8. customthe reaction mixture was evaporated
  9. custompurified by reverse phase chromatography

Sources & evidence

ORD record
ord-b8bbb49f7ee14d63afb0b128c7ca11bb
Source dataset
uspto-grants-2012_01
Patent number
US08088771B2

Reaction notes

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