Diisopropylethylamine → Benzyl {2-[({4-[(3R,4S,5S)-3-[(tert-butoxycarbonyl)amino]-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-1-yl]pyridin-3-yl}amino)carbonyl]-7-morpholin-4-ylquinolin-3-yl}carbamate

HRID 924513Notes

Reaction equation

HRID 924513 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13]([C:28]([OH:30])=O)=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[C:17]([N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1)[CH:16]=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:31][C:32]1[CH:33]=[N:34][CH:35]=[CH:36][C:37]=1[N:38]1[CH2:43][C@H:42]([CH3:44])[C@H:41]([N:45]2[CH:49]=[CH:48][N:47]=[N:46]2)[C@H:40]([NH:50][C:51](=[O:57])[O:52][C:53]([CH3:56])([CH3:55])[CH3:54])[CH2:39]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.CO.O>[C:53]([O:52][C:51]([NH:50][C@H:40]1[C@@H:41]([N:45]2[CH:49]=[CH:48][N:47]=[N:46]2)[C@@H:42]([CH3:44])[CH2:43][N:38]([C:37]2[CH:36]=[CH:35][N:34]=[CH:33][C:32]=2[NH:31][C:28]([C:13]2[C:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:21][C:20]3[C:15](=[CH:16][C:17]([N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)=[CH:18][CH:19]=3)[N:14]=2)=[O:30])[CH2:39]1)=[O:57])([CH3:54])([CH3:55])[CH3:56]

Participants

8

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 867268923-{[(Benzyloxy)carbonyl]amino}-7-morpholin-4-ylquinoline-2-carboxylic acidHCID 86726946tert-Butyl [(3R,4S,5S)-1-(3-aminopyridin-4-yl)-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-3-yl]carbamate

Product 1

HCID 86726953Benzyl {2-[({4-[(3R,4S,5S)-3-[(tert-butoxycarbonyl)amino]-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-1-yl]pyridin-3-yl}amino)carbonyl]-7-morpholin-4-ylquinolin-3-yl}carbamateYield 33.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 3-{[(benzyloxy)carbonyl]amino}-7-morpholin-4-ylquinoline-2-carboxylic acid (9.6 mg, 0.024 mmol), tert-butyl [(3R,4S,5S)-1-(3-aminopyridin-4-yl)-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-3-yl]carbamate (8.0 mg, 0.021 mmol), and HATU (26 mg, 0.07 mmol) in DMF (0.23 mL), DIPEA (0.014 mL, 0.083 mmol) was added. The reaction mixture was stirred at room temperature for 2 h. The mixture was diluted with MeOH and H2O, then filtered and purified by preparative LCMS (pH=10 method; XBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with 0.1% NH4OH) to give the sub-title compound as a bright yellow powder (5.4 mg, 33%). LCMS calc. for C40H47N10O6 (M+H)+: m/z=763.4. Found: 763.3.

Workup

  1. additionwas added
  2. filtrationfiltered
  3. custompurified by preparative LCMS (pH=10 method
  4. washXBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with 0.1% NH4OH)

Sources & evidence

ORD record
ord-33380911b0e545219bfcedaac0cdc64e
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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