Water → Ammonia

HRID 2042368Notes

Reaction equation

HRID 2042368 reaction equation
[NH2:1][C:2]1[C:3]2[N:4]([C:8]([C@H:12]3[CH2:17][CH2:16][C@H:15]([CH2:18][NH:19][C:20](=[O:29])[O:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH2:14][CH2:13]3)=[N:9][C:10]=2I)[CH:5]=[CH:6][N:7]=1.C(OC([N:37]1[C:45]2[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=2)[CH:39]=[C:38]1B(O)O)=O)(C)(C)C.O.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.COCCOC>[NH3:1].[NH2:1][C:2]1[C:3]2[N:4]([C:8]([C@H:12]3[CH2:17][CH2:16][C@H:15]([CH2:18][NH:19][C:20](=[O:29])[O:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH2:14][CH2:13]3)=[N:9][C:10]=2[C:38]2[NH:37][C:45]3[C:40]([CH:39]=2)=[CH:41][CH:42]=[CH:43][CH:44]=3)[CH:5]=[CH:6][N:7]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 27733021-(tert-Butoxycarbonyl)indole-2-boronic Acid (contains varying amounts of Anhydride)HCID 178508480HCID 178508480, compound

Product 2

HCID 222AmmoniaYield 5%HCID 178508457HCID 178508457, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of benzyl {[trans-4-(8-amino-1-iodoimidazo[1,5-a]pyrazin-3-yl)cyclohexyl]methyl}carbamate (1.00 g, 0.00180 mol), 1-(tert-butoxycarbonyl)-1H-indole-2-boronic acid (0.517 g, 0.00198 mol), 1,2-dimethoxyethane (7.7 mL), water (1.4 mL, 0.081 mol) and Cesium Carbonate (1.17 g, 0.00360 mol) degassed three times, treated with tetrakis(triphenylphosphine)palladium(0) (200 mg, 0.0002 mol) and degassed once more. The resulting mixture was heated at 100° C. overnight before being diluted with EtOAc (40 mL), washed with water (2×30 mL) and brine (20 mL) then dried over Na2SO4 and concentrated in vacuo. The crude product thus isolated was chromatographed over silica gel eluting with hexane→EtOAc:hexane: 5% 2M NH3 in MeOH 1:1:0.05 to afford the title compound. 1H NMR (400 MHz, CDCl3): δ 1.13-1.22 (m, 2H), 1.75-1.86 (m, 2H), 1.94-1.97 (m, 2H), 2.11-2.13 (m, 2H), 2.86 (m, 1H), 3.12-3.16 (m, 2H), 4.82 (m, 1H), 5.12 (s, 2H), 5.69 (br, 2H), 6.78 (s, 1H), 7.13-7.15 (m, 2H), 7.19-7.25 (m, 2H), 7.32-7.38 (m, 5H), 7.42 (d, J=8.0 Hz, 1H), 7.64 (d, J=8.4 Hz, 1H), 9.09 (br, 1H). MS (ES+): m/z 495 [MH+].

Workup

  1. customdegassed three times
  2. customdegassed once more
  3. additionbefore being diluted with EtOAc (40 mL)
  4. washwashed with water (2×30 mL) and brine (20 mL)
  5. dry with materialthen dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude product thus isolated
  8. customwas chromatographed over silica gel eluting with hexane→EtOAc

Sources & evidence

ORD record
ord-9b92dd0079354e83a9fb7a4baf3cae3b
Source dataset
uspto-grants-2013_11
Patent number
US08586546B2

Reaction notes

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