Methanol → HCID 67168742, compound

HRID 1506552Notes

Reaction equation

HRID 1506552 reaction equation
[OH:1][CH:2]([C:6]1[CH:7]=[C:8]2[C:31](=[CH:32][CH:33]=1)[C:12]1=[N:13][O:14][C:15]([C:16]3[C:20]([C:21]([F:24])([F:23])[F:22])=[C:19]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[O:18][N:17]=3)=[C:11]1[CH2:10][CH2:9]2)[C:3](O)=[O:4].CN(C(ON1N=[N:49][C:44]2[CH:45]=[CH:46]C=[N:48][C:43]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.CO>CN(C=O)C>[C:43]([C:44]1([NH:49][C:3](=[O:4])[CH:2]([OH:1])[C:6]2[CH:7]=[C:8]3[C:31](=[CH:32][CH:33]=2)[C:12]2=[N:13][O:14][C:15]([C:16]4[C:20]([C:21]([F:22])([F:23])[F:24])=[C:19]([C:25]5[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=5)[O:18][N:17]=4)=[C:11]2[CH2:10][CH2:9]3)[CH2:46][CH2:45]1)#[N:48]

Participants

6

Reactant 4

HCID 887MethanolHCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67170876HCID 67170876, compound

Product 1

HCID 67168742HCID 67168742, compoundYield 38.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 2-hydroxy-2-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)acetic acid (Preparation 131B, Isomer 2, 25 mg, 0.055 mmol) in DMF (1 mL) was added 1-aminocyclopropanecarbonitrile, HCl (9.74 mg, 0.082 mmol), HATU (24.99 mg, 0.066 mmol), and N-methylmorpholine (0.036 mL, 0.329 mmol). The reaction mixture was stirred for 1 h at room temperature. Methanol was added and it was purified by prep HPLC (Phenomenex 21.2×250 mm, Solvent A: 90% water with 10% MeOH and 0.1% TFA, Solvent B: 90% MeOH with 10% water and 0.1% TFA, Gradient: 0% B to 100% B over 30 min, 20 mL/min, 220 nM) to yield N-(1-cyanocyclopropyl)-2-hydroxy-2-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)acetamide (11 mg, 0.021 mmol, 38.2% yield) as a white solid: product HPLC ret. time=9.96 min (condition G); LC/MS M+1=521.06; 1H NMR (400 MHz, DMSO-d6) δ ppm 9.06 (1H, s), 7.89 (1H, d, J=7.92 Hz), 7.80 (2H, d, J=7.26 Hz), 7.63-7.76 (3H, m), 7.41-7.51 (2H, m), 6.43 (1H, d, J=4.18 Hz), 5.02 (1H, d, J=3.74 Hz), 3.05 (4H, s), 1.46 (2H, q, J=2.79 Hz), 1.07-1.24 (2H, m).

Workup

  1. customit was purified by prep HPLC (Phenomenex 21.2×250 mm, Solvent A: 90% water with 10% MeOH and 0.1% TFA, Solvent B: 90% MeOH with 10% water and 0.1% TFA, Gradient: 0% B to 100% B over 30 min, 20 mL/min, 220 nM)

Sources & evidence

ORD record
ord-f7512556dd184de596dcf1b77d51d65d
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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