4-Methylmorpholine → HCID 57389280, compound

HRID 1427430Notes

Reaction equation

HRID 1427430 reaction equation
[CH3:1][CH:2]([CH3:31])[CH2:3][CH:4]([NH:21][C:22]1[CH:30]=[CH:29][C:25]([C:26]([OH:28])=O)=[CH:24][N:23]=1)[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)=[CH:7][CH:6]=1.CC(S(N)=O)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.CN1CCOCC1.[NH:70]1[C:74]([CH2:75][NH2:76])=[N:73][N:72]=[N:71]1>CN(C)C=O>[N:70]1[NH:71][N:72]=[N:73][C:74]=1[CH2:75][NH:76][C:26](=[O:28])[C:25]1[CH:29]=[CH:30][C:22]([NH:21][CH:4]([C:5]2[CH:6]=[CH:7][C:8]([C:11]3[CH:16]=[CH:15][C:14]([C:17]([F:19])([F:20])[F:18])=[CH:13][CH:12]=3)=[CH:9][CH:10]=2)[CH2:3][CH:2]([CH3:1])[CH3:31])=[N:23][CH:24]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 3382465Tert-ButanesulfinamideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67981036HCID 67981036, compoundHCID 178510704HCID 178510704, compound

Product 1

HCID 57389280HCID 57389280, compoundYield 8.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A 5 mL vial equipped with a stir bar was charged with 6-(3-methyl-1-(4′-(trifluoromethyl)biphenyl-4-yl)butylamino)nicotinic acid (0.100 g, 0.233 mmol) as prepared in Example 1.1 using racemic 2-methylpropane-2-sulfinamide in Step B, O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyl uronium hexafluorophosphate (133.0 mg, 0.350 mmol), N-methylmorpholine (118.0 mg, 1.167 mmol), N,N-dimethylformamide (1.2 mL). The mixture was purged with nitrogen, heated to 50° C. and stirred for 30 minutes. Then, (1H-tetrazol-5-yl)methanamine (39.9 mg, 0.233 mmol) was added. The mixture was stirred at 50° C. overnight. The reaction mixture was purified by prep-HPLC to give (+/−)-N-((2H-tetrazol-5-yl)methyl)-6-(3-methyl-1-(4′-(trifluoromethyl)biphenyl-4-yl)butylamino)nicotinamide (10 mg, 4.2%) as a white solid. 1H NMR (400 MHz, CD3OD, δ): 8.50 (d, 1H), 7.86 (dd, 1H), 7.80 (d, 2H), 7.72 (d, 2H), 7.64 (d, 2H), 7.50 (d2H), 6.58 (d, 1H), 5.11 (m, 1H), 4.82 (s, 2H), 1.89-1.82 (m, 1H), 1.80-1.72 (m, 1H), 1.68-1.62 (m, 1H), 1.03 (d, 3H), 1.00 (d, 3H) ppm. MS (M+1): 510.3

Workup

  1. customA 5 mL vial equipped with a stir bar
  2. customThe mixture was purged with nitrogen
  3. stirringThe mixture was stirred at 50° C. overnight
  4. customThe reaction mixture was purified by prep-HPLC

Sources & evidence

ORD record
ord-48f446a66c0a498f8c3aa6af51272b11
Source dataset
uspto-grants-2015_01
Patent number
US08933104B2

Reaction notes

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