5-Fluoroindole-2-carboxylic acid → HCID 25174432, compound

HRID 549451Notes

Reaction equation

HRID 549451 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([OH:13])=O)=[CH:5]2.[NH2:14][C@H:15]1[C:23]2[C:18](=[CH:19][CH:20]=[C:21]([C:24]#[N:25])[CH:22]=2)[CH2:17][C:16]1([CH3:27])[CH3:26].CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>CN(C=O)C>[C:24]([C:21]1[CH:22]=[C:23]2[C:18]([CH2:17][C:16]([CH3:27])([CH3:26])[C@H:15]2[NH:14][C:11]([C:6]2[NH:7][C:8]3[C:4]([CH:5]=2)=[CH:3][C:2]([F:1])=[CH:10][CH:9]=3)=[O:13])=[CH:19][CH:20]=1)#[N:25]

Participants

6

Reactant 4

HCID 18205-Fluoroindole-2-carboxylic acidHCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 67081572HCID 67081572, compound

Product 1

HCID 25174432HCID 25174432, compoundYield 76.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 5-fluoro-1H-indole-2-carboxylic acid (56.0 mg, 0.312 mmol), (R)-3-amino-2,2-dimethyl-2,3-dihydro-1H-indene-5-carbonitrile (39.0 mg, 0.209 mmol), BOP reagent (180 mg, 0.407 mmol), N-methylmorpholine (0.13 mL, 1.18 mmol) in DMF (0.5 mL) was stirred at 50° C. for 2 hr. The desired title product (55.6 mg, 76% yield) was isolated as a white solid by prep. HPLC. LCMS (M+H)+=348.33. 1H NMR (500 MHz, DMSO-d6) δ: 11.7 (s, 1H), 8.58 (d, J=8.8 Hz, 1H), 7.70 (d, J=7.7 Hz, 1H), 7.62 (s, 1H), 7.46 (d, J=7.7 Hz, 1H), 7.44 (dd, J=8.8, 5.0 Hz, 1H), 7.39 (d, J=9.9 Hz, 1H), 7.28 (s, 1H), 7.04 (t, J=9.35 Hz, 1H), 5.37 (d, J=9.35 Hz, 1H), 2.87 (dd, J=22.0, 16.5 Hz, 2H), 1.21 (s, 3H), 0.94 (s, 3H).

Sources & evidence

ORD record
ord-3dcbc57316c04dd188bdc20de950504c
Source dataset
uspto-grants-2011_05
Patent number
US07943658B2

Reaction notes

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