Dimethylformamide → HCID 131720606, compound

HRID 1599066Notes

Reaction equation

HRID 1599066 reaction equation
[NH2:1][CH:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([N:13](C(C)C)C2C=CC(OC)=CC=2)=[O:12])[C:6]2[CH:25]=[CH:26][CH:27]=[CH:28][C:5]=2[N:4]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=2)[C:3]1=[O:35].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)[C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][C:46]=2N=N1.[CH:63]1C=CC2N(O)N=N[C:67]=2[CH:68]=1.[NH:73]1[C:81]2[C:76](=[CH:77][CH:78]=[CH:79][CH:80]=2)[CH:75]=[C:74]1[C:82]([OH:84])=O.CN([CH:88]=[O:89])C>CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[CH:68]([C:10]([C:50]1[CH:51]=[CH:46][C:47]([O:89][CH3:88])=[CH:48][CH:49]=1)([C:11](=[O:12])[NH2:13])[N:7]1[C:8](=[O:9])[CH:2]([NH:1][C:82]([C:74]2[NH:73][C:81]3[C:76]([CH:75]=2)=[CH:77][CH:78]=[CH:79][CH:80]=3)=[O:84])[C:3](=[O:35])[N:4]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=2)[C:5]2[CH:28]=[CH:27][CH:26]=[CH:25][C:6]1=2)([CH3:67])[CH3:63]

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 72899Indole-2-carboxylic acidHCID 757711-HydroxybenzotriazoleHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 18929586HCID 18929586, compound

Product 1

HCID 131720606HCID 131720606, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-(3-Amino-2,4-dioxo-5-pyrdin-2-yl-2,3,4,5-tetrahydrobenzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide (276 mg), BOP (244 mg), HOBT (78 mg), DMAP (69 mg) and indole-2-carboxylic acid (98 mg) in DMF (1 ml) was stirred at rt for 18 h. The reaction mixture was diluted with ethyl acetate (15 ml), washed with 1N aqueous sodium hydroxide solution (2×15 ml), water (20 ml), brine (20 ml), dried (K2CO3) and concentrated in vacuo to afford the cude product. Purification by RP-HPLC utilizing a linear gradient (20% A, 80% B to 90% B, 10% C, 30 min) gave the title product (26.6 mg) as a white lyophile;Tr=21.3 min. 1H NMR (300 MHz, CDCl3); 0.98 (2×d, J=7 Hz, 6H), 3.68 (s, 3H), 4.17 (d J=16.6 Hz, 1H), 4.37 (d, J=16.8 Hz, 1H), 4.87 (sept, J=6.8 Hz, 1H), 5.40 (d, J =6.8 Hz, 1H), 6.40 (d, J=5.3 Hz, 1H), 6.75-6.84 (m, 5H), 6.92-6.99 (m, 2H), 7.07 (t, J=7.3 Hz, 1H), 7.09-7.2 (m, 4H), 7.24 (t, J=9.2 Hz, 1H), 7.40 (t, J=9.1 Hz, 2H), 7.52 (d J=7.9 Hz, 1H), 7.72 (m, 2H), 8.38 (d, J=4.4 Hz, 1H), 9.19 (s, 1H). m/z [MH]+ =617.

Workup

  1. washwashed with 1N aqueous sodium hydroxide solution (2×15 ml), water (20 ml), brine (20 ml)
  2. dry with materialdried (K2CO3)
  3. concentrationconcentrated in vacuo
  4. customto afford the cude product
  5. customPurification by RP-HPLC
  6. customa linear gradient (20% A, 80% B to 90% B, 10% C, 30 min)

Sources & evidence

ORD record
ord-a7cf7e02f8d04b98abc053292cf44d54
Source dataset
uspto-grants-1998_04
Patent number
US05739129

Reaction notes

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